FUSED AROMATIC OXAZEPINONES AND SULPHUR ANALOGUES THEREOF AND THEIR PREPARATION AND USE IN COUNTERACTING HISTAMINE

Abstract: Aromatic-2,3-dihydro-1,4-oxazepin-5(4H)-ones and sul­ phur analogues thereof having the formula wherein B and E are oxygen and/or sulphur, n is 1, 2 or 3, Z is -NR¹R², 1H-pyrazol-1-yl or 1H-imidazol-1-yl and R is loweral­ kyl, cycloalkyl or phenylloweralkyl having antihistaminic application, a process for the preparation thereof, and intermediates therefor are disclosed.

Description: FUSED AROMATIC OXAZEPINONES AND SULPHUR ANALOGUES THEREOF AND THEIR PREPARATION AND USE IN COUNTERACTING HISTAMINE The present invention relates to novel aromatic 2,3-dihydro-1,4-oxazapin-5-(4H)-ones and Sulphur analogues. thereof and is particularly concerned with aromatic-2,3- dihydro-1,4-oxazepin-5(4H)-ones and sulphur analogues thereof which have the aromatic component fused into the oxazepine or thiazepine ring and are substituted in the 2-position with short chain aminoalkyl radicals, having antihistaminic and anti-allergy utility and a nove@ process and novel intermediates for the preparation thereof. 3-Aryl-1,4-benzoxazepin-5(4H)-ones substituted on the oxazepine nitrogen by an aminoalkyl radical have been disclosed by Schenker, K. in Swiss Patent 505.850 (C.A. 75, 98600s). Conversion of flavanones into benzoxazepinones substituted in the 2-position by a phenyl radical has been disclosed by Levai, A. and Bognar, R., Top. Flavanoid Chem. Biochem. Proc. Bung. Bioflavonoid Symp. 4th Ed. 1973 (Pub. 1975) 119-23 (C.A. , 79098n). Thione derivatives were obtained by treating with phosphorus pentasulphide. Certain chemical intermediates, the 1-substituted- 3-substituted phenoxypyrrolidines illustrated by 1-methyl-3-(2-carbamoylphenoxy)pyrrolidine, 1-benzyl-3-(2-carbamoylphenoxy)pyrrolidine, and 1-methyl-3-(2-carboxyphenoxy)pyrrolidine in an otherwise novel class are disclosed in U. S. Patent 3,577,415. According to a first aspect of the present invention, there is provided an oxazepine or thiazepine derivative having the formula: EMI2.1 wherein A represents an aromatic ring system having two of its carbon atoms held mutually with the oxazepine or thiazepine moiety selected from benzene, naphthalene or a pyridine in any of its four positions. any of the rings being optionally suuti'tuLed by one or two Y radicals selected from halo, lower- # alkyl, loweralkoxy, nitro and trifluoromethyl; B and E are selected from oxygen end sulphur and may be the same or different; R is selected from hydrogen loweralkyl, cycloalkyl or phenyl-loweralkyl, of which phenyl is optionally substituted by one or two radicals selected from halo, loweralkyl, loweralkoxy, nitro or trifluoromethyl; n is 1, 2 or 3; 12 W Z is selected from -N W RS 1H-pyrazol-1-yl and 1H-imidazol-1-yl; each of R1 and RS is selected from the group consisting of hydrogen, loweralkyl, cycloalkyl and phenyl-loweralkyl, of which phenyl is # optionally substituted by I or 2 radicals-selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyland cyano, or RÚ and Rê taken together with the adjacent nitrogen atom may form a heterocyclic residue selected from 1-pyrrolidin-1-yl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl, 1-piperidinyl, 4-substituted piperidine-1-yl, 4-morpholinyl, l-piperazinyl, 4-substituted piperazin-l-yl and 1,2,3,6- tetrahydropyridin-1-yl and the pharmaceutically acceptable salts thereof wA the proviso that when R = R, Z is never a primary or secondary amine, and a further proviso that when n = 3, Z is not 1H-pyrazol-1-yl, 1H-imidazol-1-yl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl or 1,2,3,6-tetrahydropyridin-1-yl. Preferred compounds of Formula 1 are those in etch: the ring represented by A is substituted by cone or more chlorine or braaine arans or by a methoxy group; R represents a methyl, ethyl, benzyl or hexyl group; and/or Z represents a dimethylamino group. According to a second aspect of the invention, there is provided a compound as defined above for use in medicine, which may be pharmaceutical or. veterinary medicine, especially as an antihistamine. In the further definition of symbols in the formulas hereof and where they appear elsewhere throughout this specification and the claims, the terms have the following significance. The term "loweralkyl" äs used herein includes straight and branched chain radicals of up to eight carbons inclusive and is exemplified by such groups as methyl, ethyl, propyl1 isopropyl, butyl, sec. butyl, tert.butyl, amyl, isoamyl, hexyl, heptyl and octyl radicals and the like. The term "loweralkoxy" has the formula -O-loweralkyl. The term "cycloalkyl" as used herein includes primarily cyclic alkyl radicals containing 3-9 carbon atoms inclusive and includes such groups as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl, cycloheptyl and the like. The terms "halo" or "halogen" when referred to herein include fluorine, chlorine, bromine and iodine unless otherwise stated. "Phannaceutically'acceptable salts" include acid addition salts, hydrates, alcoholates and quaternary salts of the compounds of Formula I, which are physiologicallycompatible in warm-blooded animals. The acid addition salts may be formed by either strong or weak acids. Representative of strong acids are hydrochloric, sulphurice - and phosphoric acids. Representative of weak acids are fumaric, maleic, succinic, oxalic, citric, tartaric, cyclohexamic and the li4. Suitable quaternary salts include the loweralkyl halides and loweralkyl sulphates. As used herein, the word "aromatic", when used to qualify such terms as "ring" and "ring system" should not be taken to imply that the ring or ring system as the case may be is necessarily composed entirely of carbon atoms. It will therefore be understood that certain heterocyclic rings and ring systems fall within the definition of "aromatic". By sulphurizing agent" is meant any agent or mixture of agents which will convert ox- and thiazepinones to ox- and thiazepine-thiones, such as 2,4-bis(4-methoxy phenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulphide or a mixture of # - phosphorus pentasiphide and alkalimetal sulphide or a mixture of phosphorus pentasulphide in pyridine. The compounds of the present invention exhibit antihistaminic activity in guinea pigs; -The method of testing is a modification of the procedure oT Tozzi et al.(Agents and Actions, Vol. 4/, 264-270, 1974) as follows: Guinea pigs are fasted 18-24 hrs in individual cages. Water is available ad libitum. On the tst day, animals in groups of 3 are injected intraperitoneally with 30 mg/kg of the test compound prepared in an appropriate vehicle. Thirty minutes later histamine at a dosage level of 1.2 mg/kg (= 2 x the LDss) is injected into a marginal ear vein. Survival of the guinea pigs for 24 hrs is positive evidence of antihistamine activity. If the vehicle used for the test compound is other than water, its effect is established by testing an equal amount as a control. The dose protecting 50% of the animals (PD50) from death may be established from dose-response curves. According to a third aspect of the invention, there is provided a process for the preparation of a compound or salt in accordance with the first aspect, the process comprising either i) reacting a compound of the formula EMI6.1 wherein A,B,E,R,Y and n are as defined for formula I and X represents chlorine, bromine or cyano with a compound- of the formula ZH wherein Z is as defined for formula I;.or i reducing a compound of the formula EMI6.2 to give a compound.of formula I in which represents oxygen, Z represents-NH2 and n is 2 or 3, and if necessary iii) converting a compound of fornula I so formed into another.-compound of formula I; and optionally iv) preparing a pharmaceutically acceptable salt of a compound so formed. The preferred novel process of this invention comprises the following steps: Step 1) Halogenating a compound of the formula EMI7.1 wherein; A represents an aromatic ring selected from benzene, naphthalene, or a pyridine in any one of its four positions, optionally substituted by one or two Y-radicals selected from halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl; Z is oxygen or sulphur; R is selected from loweralkyl; ¯ cycloalkyl and phenyl-loweralkyl, of which phenyl may be optionally substituted by one or two radicals selected from halo, loweralkyl, loweralkoxy, nitro andtrifluoromethyl; ; R3 is hydrogen or an acid neutralizing ion, and n is one or two, to give a compound of the formula EMI8.1 or its free base wherein X is chlorine or bromine and A, E, R, Y and n are the same as the starting values.. Among suitable halogenating agents are a) thionyl halides b) triphenylphosphine and a carbon tetrahalide c) phosphorus pentahalides d) phosphorus trihalides, and e) triphenylphosphine dihalide, with the thionyl halides being preferred. Step 2) Neutralizing, if necessary, and fusing the carboxylic acid halide derivative prepared in step 1 to give an oxazepinone or a thiazepinone of the formula EMI8.2 wherein A, E, R, X, Y and n are as defined above in step 1, and A now has two of its carbon atoms held mutually with the oxazepine or thiazepine moiety. Step 3) Optionally reacting the compound prepared in step 2 with a sulphurizing agent to obtain an oxazepinethione or a thiazepinethione of the formula EMI9.1 wherein A, Z, R, X, Y and n are as defined above in step 2. Step 4) When required, reacting a compound prepared in step 2 with an alkali-metal cyanide to obtain a compound of the formula. EMI9.2 wherein A, E, Y, and R are as defines in step 2. Step 5) Reacting a halogen compound prepared in step 2 or 3 with a compound of the formula ZE' wherein Z is selected from -NR1, 1H-pyrazol-1-yl and lR-imidazol-l-yl, and wherein R1 and Rê are selected from hydrogen, loweralkyl, cycloalkyl and phenyl-loweralkyl, of which phenyl may be optionally substituted with 1 or 2 radicals selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl ahS cyano, or RÚ and R2 taken together with the adjacent nitrogen atom may form a heterocyclic residue selected from l-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl, 1-piperidinyl, 4-substituted-piperidine-1-yl, 4-morpholinyl, l-piperazinyl, 4-substituted-piperazin-1-yl and 1,2,3,6tetrahydropyridine-l-yl, to give a compound of the formula EMI9.3 wherein A, E, R, n and Y are as defined above in step 2, Z is the same as in the ZH compound, and B is an oxygen or sulphur@ atom. Step 6) Optionally reacting a compound prepared in step 5 wherein B is an oxygen atom with a sulphurizing agent, preferably phosphorus pentasulphide. in pyridine to obtain a compound of the formula EMI10.1 wherein A, E, R, n, Y and Z are as defined in step 5.. Step 7) Reducing cyano compound (Formula IIc) prepared in step 4 to a primary nmine of the formula EMI10.2 wherein A, E, Y and R are defined in steps 2 and 4, Step 8) when required, reacting a primary amine prepared in steps 5 or 7 of the formula EMI10.3 wherein A, E, Y and R are as defined in step 2 (R is not hydrogen) with one of the following reactants or sets of reactants a) formaldehyde and formic acid to give a tertiary dimethylamine, b) a halide to give a heterocyclic amine, c) a dialdehyde and sodium'cyanoborohydride to give a heterocyclic amine, d) equal molar amounts of aldehyde or ketone, sodium cyanoborohydride with large excess of above primary amine to give a secondary amine, e) equal nolar'auounts of the p primary amine and sodium cyanoborohydride with at least two equivalents of aldehyde or ketone to give a tertiary amine, f) in sequence trifluoroacetyl chloride, alkyl or phenyl alkyl halide, potassium hydride and potassium hydroxide to give.a. secondary amine, all products being encompassed by the formula EMI11.1 wherein A, E, E, Y.and R are as defined in step 2 (note: R is not. hydrogen) and Z is -NR122 2 wherein each of R1 and 1 Rê is lower- alkyl, cycloalkyl or phenyl-loweralkyl with phenyl being optionally substituted by halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl or cyano or R1 and R2 taken together with the adjacent nitrogen may form a heterocyclic residue selected from 1-pyrrolidinyl, 1-piperidinyl, 4-substituted piperidin-l-yl, 4-morpholinyl, l-piperazinyl-l-yl and 1,2,3,6-tetrahydropyridin-1-yl and optionally sulphurizing the azepinone or thiazepinone to give the corresponding thione as in step 6. Step 9) when required, reacting a benzyl or substituted benzyl compound obtained in steps 5, 6 or 8 wherein Z is tertiary amino, pyrazolyl or imidazolyl of the formula EMI12.1 wherein A, E and Y are as defined in step 2, and Z is any radical taken from the definition of Z under Formula I, subject to the same provisos given thereunder, and with sodium and ammonia to give a compound of the formula EMI12.2 wherein A, E and Y-are as defined in step 2, n is 1 to 3- and Z is as defined under Formula I with limitations given thereunder. Step 10) 'Optionally reacting the free base of any compound prepared in steps 5 to 9 with a pharmaceutically acceptable acid or quaternary forming halide or sulphate to form a pharmaceutically acceptable salt thereof. The compounds of Formula I wherein n is 2 are preferred for their antihistaminic activity. The process which includes steps 1 to 3,-5, 6 and 10 wherein compounds prepared have a methyl or ethyl side chain (n = I or 2) represents a preferred process corresponding to a succession of steps designated A to F as explained hereinbelow. The compounds of Formulas Ia, Ib, Ic-1 to Ic-7, Ic-1a, Id, IeX If are all encompassed by Formula I and the compounds of Formulas IIa, Ilbi IIc, 11d and IIe are all encompassed by Formula II. Steps 1 to 4 also represent a novel process for preparing compounds of Formula IIa, IIb, IIc, all encompassed by Formula II The present invention provides certain novel aromatic 2,3-dihydro-1,4-oxazepin 5(4H)-ones (and sulphur analogues thereof)substituted in the 2-position with short chain aminoalkyl radicals which have antihistaminic activity. -The invention also provides @ certain novel aromatic 2,3-dihydro-1,4-oxazepin-5(4H)-ones (and sulphur analogues thereof) substituted in the 2-position with alkyl halo or alkyl cyano radicals which are chemical intermediates. The novel oxazepine and thiazepine precursors leading to compounds of Formula I constitute a fourth aspect of the invention and have the formula: EMI13.1 wherein A, B, E, R and Y are as defined under Formula I above except R is not hydrogen, n is 1 or 2, and X is chlorine, bromine or cyano, and the acid addition salts, thereof. The invention further provides a novel route and process for preparation of aromatic 2,3-dihydro-1,4- oxazepin-5(4H)-ones (and sulphur analogues thereof) substituted in the 2-position with short chain alkylhalo or alkylcyano or alkylamino radicals. According to a fifth aspect of the invention, there is provided a process for the preparation of a compound of the formula: EMI14.1 wherein: A selected from an aromatic ring system having twoof its carbon atoms held mutually with the oxazepine or thiazepine moiety selected from benzene, a naphthalene, a pyridine in any of its four positions, any of which ring systemsis optionally substituted by one or. two Y radicals selected from halo, loweralkyl, loweralkoxy, nitro or trifluoromethyl; ^ B and E are selected from oxygen and sulphur and may be the same or different; R is selected from loweralkyl, cycloalkyl or phentl- loweralkyl wherein phenyl is optionally substituted-by one or two radicals selected from halo, -loweralkyl, loweralkoxy, nitro or trifluoromethyl: : n is 1 or 2; X is chlorine, bromide-or cyano or an acid addition salt thereof, the process comprising i) al fusing a compound having the formula EMI14.2 wherein x represents chlorine or bromine and A,E,n,R and Y are as defined above; b) and when required reacting the compound so formed with a sulphurizing agent to obtain an oxazepinethione or a thiazepinethione; and c) optionally reacting a compound obtained in step i)a) or i)b) with an alkali metal cyanide to obtain the corresponding compound in which X represents CN; or ii) halogenating a compound obtained in step i)a), i)b) or i)c) having the formula EMI15.1 wherein E and R are as defined above, and X is chlorine, bromine or cyano with sulphuryl chloride in a suitable solvent to obtain a compound having the formula EMI15.2 wherein E and R are as defined above X is chlorine, bromine or cyano. In a preferred embodiment, the process of the fifth aspect comprises the steps of: Step i) halogenating a compound of the formula EMI16.1 wherein A, E, R, n and Y are as defined above except the two carbon atoms of A are not bound by oxazepine' or thiazepine rings and-R3 is hydrogen or an acid salt neutralizing ion, to give an acid halide of the formula EMI16.2 or its free base wherein X i5 chlorine or bromine and A, E, n, R and Y are as defined above. Step 2) fusing the compound prepared in Step 1 to give an oxazepinone or thiazepinone of the formula EMI16.3 wherein A, E, X, X,, n and Y are as defined above in Step 1 and A now has 2 of its carbon atoms held mutually with the oxazepine or thiazepine moiety. Step 3) when required, reacting the compound prepared in Step 2'with a sulpharizing agent to obtain an oxazepinethione or thiazepinethione of the formula EMI17.1 wherein A, E, R, X, Y and n are as defined ,above. - Step 4) when required, reacting a compound prepared in Step 2 with an alkali-metal cyanide to obtain a compound of the formula EMI17.2 wherein A, E, Y and R are as defined in Step 2. Step 5) in the alternate halogenating a compound prepared in Steps, 2 'or 4 having the formula EMI17.3 wherein E and R are as defined above and X is chlorine, bromine or cyano with sulfuryl chloride in a suitable solvent to give a compound having the formula EMI18.1 wherein E and R are as defind above and X is chlorine, bromine or cyano. Other chemical intermediates in the preparation of compounds of Formula II are novel They consitute ¯ a sixth aspect of the invention and have the formula EMI18.2 Formula III wherein A, E, R, n and # are as defined under Formula II above and X is chlorine or bromine. Still other chemical intermediates leading to compounds of Formula IVb have the formula: EMI18.3 formula NJa wherein A, E, R, n and Y are as defined under Formula II, and Q is selected from EMI19.1 -CN and EMI19.2 where R3 is H, alkali metal ion or an esterifying radical. Compounds of Formula IVa are novel except wherein A is phenyl or substituted phenyl and E is oxygen. These novel compounds constitute a seventh aspect of the invention. Additional objects and advantages of the present invention will be apparent one skilled in the art and others will become apparent from the following description of preferred features of the er.cent invention and from the appended claims. The present invention encompasses the novel oxazepine and thiazepine derivatives set forth in Formulas I an II and certain novel compounds of Formulas III, IVa and IVb as composition of matter and a process for the preparation of compounds of Formulas I, II and IIZ. Charts I and II illustrate the preparation of all intermediates. R is never hydrogen. Chart III illustrates reaction sequence for preparing end-products wherein R is other than hydrogen and n is 1 or 2. Chart IV illustrates preparation of compounds having 2¯positioned ethyl and propyl radicals-omega substituted by primary amine (-NEi). R is never hydrogen. Chart V illustrates methods of converting the omega SHi-substituted ethyl and propyl compounds to secondary and tertiary amines. This is analternative method for preparing the ethyl-secondary and tertiary amines. R is never hydrogen. Chart VI illustrates preparation of compounds wherein R is hydrogen. Preparations 1-23 illustrate syntheses of ,compounds 'of Formulas IVa, IVb or provide certain starting materials therefor. Intermediates 1-3i6 (see also Table 1) illustrate preparation of compounds encompassed by Formula II, which are aromatic-2,3-dihydro-1,4-oxazepin-4(4H)-ones (and sulphur analogues thereof) substituted in the 2-position with alkylhalo or alkylcyano radicals. The compounds of Formula III are formed in the reaction mixtures usually without isolation. Examples 1-71 (see also Table 2) illustrate preparation of' compounds encompassed by Formula I. The scope of the invention is not limited by the preparations, intermediates and examples, however. CHART I Preparation of Intermediates (a)(b) EMI21.1 <tb> ;- <SEP> g <SEP> òr <SEP> ) <SEP> n <tb> <SEP> &num; <SEP> t <SEP> )n <tb> <SEP> ax <tb> <SEP> Bydlrolyze <tb> <SEP> n <tb> <SEP> ( <SEP> Y) <SEP> 0- <SEP> sORs <SEP> IVb <tb> <SEP> o-2 <tb> <SEP> ; <SEP> Slogenate <tb> <SEP> w;' <SEP> ffn <tb> <SEP> 1Cx <SEP> <tb> <SEP> flX <tb> <SEP> R <SEP> 1o <tb> <SEP> nsutrlirt <SEP> whcn <SEP> squired <tb> <SEP> )-halo <tb> <SEP> &num; <SEP> s <SEP> t <SEP> CX2 <SEP> ) <SEP> zl- <SEP> h- <SEP> l <SEP> o <SEP> +° <tb> <SEP> suiphurizing <SEP> A <tb> <SEP> (yg <SEP> Agent <SEP> wiz <tb> <SEP> R <SEP> 12a <tb> <SEP> t- ptionsl <SEP> to <tb> Pootnotta: <SEP> lengthen <SEP> chain <tb> <SEP> is <SEP> never <SEP> hydrogen. <tb> <SEP> -, <SEP> I <SEP> or <SEP> P. <tb> <SEP> X <SEP> - <SEP> Halogen <SEP> (C <SEP> r) <tb> <SEP> W <SEP> - <SEP> Acryl <SEP> whonatefa-1kyl <tb> <SEP> sulfon <SEP> or <SEP> or <SEP> neutralizing <SEP> (CEE)n-CN <tb> <SEP> X <SEP> - <SEP> Acid <SEP> neutr <SEP> ion, <SEP> ion, <tb> <SEP> e.g <SEP> .9alali-xtai <tb> <SEP> Q <SEP> is <SEP> -C-SH2, <SEP> -CH, <SEP> -C-ORJ <SEP> ¯' <tb> <SEP> where <SEP> R5 <SEP> is <SEP> H, <SEP> X <SEP> or <SEP> <SEP> R <SEP> ISz <tb> <SEP> esterifying <SEP> radical. <tb> <SEP> BydrolytX <SEP> when <SEP> Q8iv <SEP> other <tb> <SEP> than <SEP> R <SEP> or <tb> <SEP> *D4agstm <SEP> illustrttsng <SEP> the <tb> <SEP> suggested <SEP> formation <SEP> and <tb> <SEP> cleavage <SEP> of <SEP> bonds <SEP> to <tb> <SEP> effect <SEP> rearranct:nent. <tb> <SEP> "¯* <SEP> tt+,CBe <SEP> r <SEP> O <tb> <SEP> '1 <SEP> ;p <tb> <SEP> bx <SEP> 1 <tb> CHART II Alternate Method of Preparing Pyrwdo Ring Halogenated Intermediate a EMI22.1 Footnotes: X = CI, Br, CN E and-R are as defined in Formula I a) n = 1 or 2 CHART III Preparation of End Products (n = 1 or 2; R = other than H) EMI22.2 Footnote: Z is as defined for n = 1 or 2 under Formula I. CHART IV Preparation of Primary Ethyl and Propyl Amino Compounds wherein R is other than Hydrogen from Cyano Intermediate EMI23.1 CHART VI Preparation of Compounds Having Unsubstituted Azepine Nitrogen (R=H) EMI23.2 R = Benzyl R = H Footnote: *Z cannot be a primary or secondary amine. CHART V Additional Preparations of Secondary and Tertiaryl Amino-alkyl Compounds wherein R is other than H EMI24.1 <SEP> o1 <SEP> 5 <tb> (Y <SEP> Y, <SEP> (caJ: <tb> <SEP> d <SEP> K 8 <tb> <SEP> Zc1 <SEP> <tb> <SEP> -. <tb> <SEP> * <SEP> d±±4,, <SEP> II <SEP> Sat,' <tb> <SEP> i <SEP> E(Y) <tb> <SEP> z <SEP> SaBS <SEP> (Y) <tb> cH3OR <SEP> pE <SEP> 68) <SEP> t <SEP> 02 <SEP> R <SEP> 1 <SEP> c-3 <tb> <SEP> (CEc),-N-R' <tb> <SEP> I <SEP> LDlb <SEP> LLfdfhydt <SEP> Or <SEP> ketona <tb> <SEP> 1 <SEP> lt <SEP> aRCN <SEP> A <tb> <SEP> 1 <SEP> molt <SEP> per <tb> <SEP> z-l <SEP> in <SEP> o-tl <SEP> excess <SEP> 0-2 <SEP> I <tb> <SEP> OR <tb> <SEP> I <SEP> nolo <SEP> iame <SEP> or <tb> <SEP> different <SEP> aldehyde <tb> <SEP> or <SEP> ketone: : <tb> <SEP> 1 <SEP> 1 <SEP> rnle <SEP> aBR <SEP> CS; <tb> <SEP> HeOR(pE <SEP> 6-8) <tb> <SEP> ,¯- <SEP> E <SEP> (CEd)n-NRlR2 <tb> <SEP> nole <SEP> aldehyde <SEP> or <SEP> ketone <SEP> K <tb> <SEP> 2 <SEP> mole <SEP> Na3EsCS <tb> <SEP> -KeOE <SEP> (pH <SEP> 6-o) <SEP> (y) <SEP> Y <tb> <SEP> O <SEP> R <tb> <SEP> H' <tb> <SEP> Reaot <SEP> in <SEP> .euence <SEP> lI <tb> <SEP> Rsact <SEP> In-repuance <SEP> = <tb> <SEP> 2 <SEP> Trifluoroacaty <SEP> chorfda <SEP> Alkyl <tb> <SEP> 3 <SEP> halide, <SEP> or <SEP> Y <SEP> 0- <SEP> , <SEP> IC-6 <SEP> rca <tb> <SEP> 4 <SEP> Metal <SEP> hydroxide, <SEP> suitable <tb> <SEP> solvent <SEP> p <SEP> alkyl <SEP> or <SEP> Bal)Eyl <tb> <SEP> Optional <SEP> to <SEP> proihca <SEP> Ic-7 <SEP> ' <tb> <SEP> to <SEP> Optional <SEP> to <SEP> produce <tb> <SEP> Ic-6) <SEP> Su-lphurizing <SEP> agent <SEP> 9i <SEP> Ic-7 <tb> <SEP> sir <tb> Footnotes: n = 1-3 Hethod described by R. F Borch, et al., J. Amer. Chem. Soc. 93, 2897(1971). Footnote Chart V continued under *. Illustration of reaction of a compound of Formul wherein Z is NH2 with aldehydes and ketones foll Reactant Z-Radical Produced 1) 1 mole acetaldehyde -NHC2H5 1 mole NaBH5CN excess primary amine 2) 1 mole acetone -NHCH(CH3)2 1 mole NaBH5CN 3 1 mole benzaldehyde -NHCH2C6H5 1 mole NaBH5CN excess primary amine (Z=NH2) 4) 1 role cyclohexanone 1 mole NaBH5CN 5) 2 mole acetaldehyde -N(C2H5)2 2 mole NaBH5CN 6) 1 mole acetaldehyde 1 mole NABH5CN excess primary amine (Z=H) followed by 1 mole formaldehyde 1 mole NaBH3CN EMI25.1 # -N(CH3)C2H5) **J. E. Norlander et al., Tetrahedron Letters 1978(50) pp 4987-4990. In reference to the processes and the process steps of the invention summarized above as they apply to the preparation of compounds of Formulas I, II and III, the following further description is applicable. In step 1, starting compounds of Formula IVb (See Chart I) bearing a carboxylic acid or an acid neutralizing ion such as an alkali-metal walt thereof on the A ring ortho to the ether-linkage as a substantially pure entity or preferably derived in a reaction mixture resulting from hydrolysis of. precursors bearing in the same ortho position, carbamoyl, cyano or carboxylic acid ester functions without substantial isolation of the carboxylic acid (or salt) compound from the reaction mixture, are treated with any suitable halogenating agent such as are described above, preferably thionyl chloride or triphenyl phosphine and carbon tetrachloride. The halogenation isconducted in any suitable organic sCtvent,-preferably a refluxing organic solvent or a refluxing halogenating -- agent such as the preferred thionyl chloride. Temperatures for the chlorination over a wide range may be employed, for example, from room temperature to l000c. or above; however, temperatures of 50-800C. are preferred, which temperatures encompass that of refluxing chloroform or thionyl chloride. When excess halogenating agent such as thionyl chloride. has been used as carrier, it is advantageously evaporated. When solvent such as chloroform is used, it may, but not necessarily, be evaporated away. In any event a solution comprising a solvent and compounds of -Formula III oruresidue comprised of Formula III compounds, all of which are confirmed by infra-red analysis is available for use in the next step. In step 2, the halogenated compounds of Formula III, prepared in step I, if 'not already in a solvent, are solubilized with organic solvent, preferably chloroform and usually neutralized or basified preferably with a tertiary amine such as triethyl amine, and then heated at a temperature and for a time sufficient to effect a fusion of the carbonyl with the basic nitrogen and cleavage of the cyclic amine and formation of the 2-(2-alkyichloro or bromo) oxazepine, or thiazepine compounds of Formula Ila, for example, in refluxing triethylamine. If the tendency to fuse is sufficiently great, theneut,ralization OC basification may be eliminated. The Formula Ila compounds may be isolated by conventional means, for example, by partitioning between a suitable organic solvent or mixture of solvents and aqueous acid or base followed by drying and evaporating the organic layer and recrystallizing the residue from a suitable solvent. In step 3, the compounds of Formula Ila may optionally be converted, to the oxazepinethione or thiazepinethione (lIb) by heating together with a sulphurizibg agent in a suitable organic solvent such as toluene. The thione (IIb) may be isolated by conventional means preferably by - partitioning between an organic solvent and dilute alkalimetal base and crystallizing from a suitable solvent such as ethanol. In step 4, an oxazepinone or thiaz,epinone (Ila) is reacted with potassium cyanide in a hot protic solvent using a phase transfer catalyst such as tetrabutyl ammonium bromide. The resulting cyano compound is then extracted, into a suitable solvent such as ethyl acetate, and the solution dried and evaporated. ' The residue is then recrystallized from suitable solvent such as a mixture of ethyl acetate and isopropyl ether or ethyl acetate alone. As will be realized, the compounds produced have methyl and ethyl cyano side chains (n = 1 or 2) which lead to side chain lengthening to amino propyl 'n = 3 or as an alternate starting material for lengthening of a methyl chain to amino ethyl. In step 5, the oxazepinone and thiazepinone (via) obtained in step 2 or the oxazepinethione and thiazepinethione (IIb) obtained in step 3 are reacted with pyrazole, imidazole or with an amine of the formula NHR1R2 wherein RÚ and Rê have the value given under Formula X above to give compounds of Formulas Ia and Ib, respectively. The latter reaction is preferably conducted in excess amine as in the instance of volatile methylamines. The free bases of products of Formula Ia and Ib are isolated by conventional means by removing volatiles and partitioning between dilute aqueous alkali metal base and a solvent such as chloroform or methylene chloride followed,by evaporation. The free base may be converted to a pharmaceutically acceptable salt with an appropriate acid and in the case of a cruaternary salt with a loweralkyl halide or sulphate and recrystallized by conventional means. The free bases may be recovered from the acid addition salts, usually in a purer form by againpartitioning the salt between aqueous base and a suitable solvent followed by evaporation. As will be realized and as shown in Chart I, the side chain of the intermediate produced is limited tÏ aminomethy.l and amino- etf-iyl (n=2). In step 6, when it is desirable, a compound prepared in step 5 wherein B is oxygen, is sulphurized preferably by refluxing in dry pyridine with phosphorus pentasulphide for several hours.- The resulting thione is isolated by cooling the solution and partitioning between a suitable solvent such as chloroform and an aqueous base and evaporating the organic phase and isolating by conventional means. In step 7, a cyano compound (lIc) prepared in step 4 which is an oxazepinone and thiazepinone is reduced, preferably with hydrogen using Raney nickel catalyst at about ¯ 60 C. The primary aminoethyl or aminopropyl compound 2 or 3) produced is isolated by conventional means, preferably as an acid addition salt which may be converted back to the free base by partitioning between a suitable solvent and aqueous base and thereafter drying and evaporating the organic layer. In step 8.(see Chart V), a primary amine is converted to a secondary or tertiary amine by a choice of reactants. The method provides a route to secondary and tertiary amino compounds of Formula I having n r 3 not afforded by step 5 and, In addition, provides an alternate route to secondary and tertiary amino compounds of Formula I wherein n = 1 or 2. The preparation of dimethylamino derivatives by reaction of primary amine with formaldehyde and formic acid is a conventional method for preparing tertiary dimethyl amines as is reaction of a halide to give a heterocyclic amine such as l-pyrrolidino, piperidino or 4-morpholino. The alternatives employing sodium cyanoborohydride follow the procedures described by R. F. torch et al, J. Amer. Chem. Soc. 93, 2897 (1971). The procedure which employs conversion to a trifluoroacetamide is described by'J. E. Norlander et al, Tetrahedron Letters, 1978 (50) pp 4987-4990. In step 9, a 4-benzyloxazepinone or thiazepinone derivative (R = Benzyl) under Formula I excluding primary or secondary amines is converted to the corresponding 4unsubstituted (R c E) oxazepinone or thiazepinone by reaction with sodium and ammonia and may be isolated as illustrated in Example 68. Step 10 is optional depending on whether the compound of Formula I is .already in the form of a pharmaceutically acceptable salt or whether it is desirable to convert to another salt or whether the free base is desired. To obtain the free base from any addition salt of Formula I, the salt is partitioned between a suitable organic solvent such as chloroform and a dilute aqueous base. The organic layer is dried and condensed to give the free base which is then, if desired, reacted with an acid described above to give the desired salt. As mentioned above, the preferred steps for reaching the preferred compounds having an ethyl side chain in the 2-position include steps 1 to 3, 5, 6 and 10 of the general process for preparing all the compounds of Formula I. Inasmuch as the compounds having a methyl side chain can be made by the same process, compounds wherein n = 1 are included in the preferred process. These steps of a preferred process are designated A to F corresponding to the numbered steps of the general process with the limited tion that n = 1 or 2 and R is other than hydrogen as follows: : Corresponding General Step Number with Preferred Process Description Pertaining Step Designation 50 n = 1 or 2 A 1 3 2 C 3 D 5 6 F 10 A preferred process for the preparation of a compound or salt in accordance with the invention therefore comprises the steps of Step A) halogenating a compound of the formula EMI30.1 wherein A represents an aromatic ring system selected from benzene, naphthalene,and- . pyridine in any of-its 4 positions, any of the rings being optionally substituted by one, or two Y radicals selected from halo, lower- alkyl, loweralkoxy, nitroand trifluoromethyl, and E, R, and n are as defined above and R3 is hydrogen or an acid salt neutralizing ion to give an acid halide of the formula EMI31.1 or its free base, wherein X is chlorine or bromine and A, E, R n and Y are the same as the starting values. Step B) fusing a compound prepared in Step A to give a compound of the formula EMI31.2 wherein A, E, R, n, X and Y are as defined above in Step A and.A now has two of its carbon atoms held mutually with the oxazepine or thiazepine oiety. Step C) optionally reacting a compound prepared in Step B with a sulphurizing agent to obtain an azepinethione of the formula EMI31.3 wherein A, E, R, n, X and Y are as defined in step 2, Step D) reacting a halogen compound prepared in Steps B or C with a compound of the formula wherein Z is selected'from -NHÚRê, lE-pyrazol-l-yland 1H- imidazol-1-yl wherein each of RÚ and Rê is selected form hydrogen loweralkyl, cycloalkyl and phenyl-loweralkyl optionally substituted on phenyl with 1 or 2 radicals selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl and cyano, oriel and R2, taken together with the adjacent nitrogen atom form a heterocyclic residue selected from pyrrolidin-1-yl, 2-methylpyrrolidin-1-yl, 1-pyperidinyl, 4-substituted piperidine-l-yl, 4-morpholinyl, 1-piperazinyl, 4-substituted piperazin-l-yl and 1,2,3,6-tetrahydropyridin- l-yl, to give a compound of the formula EMI32.1 wherein A, E, B, R, n and Y are as defined in step B and Z is the same as in the ZH compounds Step E) optionally reacting a compound prepared in Step D, wherein B is an oxygen atom with a sulphurizing agent to obtain a compound of the formula EMI33.1 wherein A, E, R, Z, n and Y are as defined above, and Step F) optionally reacting a free base of any compound prepared in Steps D or-E with a) a pharmaceutically acceptable'acid, b) a loweralkylhalide, or c) a loweralkyl sulphate to form a pharmaceutically acceptable salt thereof. preparation 1 2-(1-Benzyl-3-pyrrolidinyloxy)benzami To a suspension of 11.3 g (0.11 mole) of sodium amide in 60 ml of dry toluene was added 19.3 g (0.11 mole) of l-benzyl-3-pyrrolidinol at a rate to maintain a temperature of 35OC. Stirring was continued at room temperature for 3 hours. To the mixture was added at rapid drop 19 g (0.1 mole) of o-toluenesulp'ony1 chloride with ice bath cooling to maintain a temperature of 20-300C.- Stirring was continued at room temperature for 2.5 hours and the mixture allowed to stand overnight. The toluene was washed twice with water, dried with sodium sulphate and concentrated. To a suspension of 5.4 g (0.1 mole) of sodium methoxide in 50 ml of dimethylformamide in another vessel was added 13.6 g (0.1 mole) of salicylamide in 75 ml of dimethylformamide at a rate to maintain a temperature of 50 C. After stirring 15 minutes, the above prepared sulphanate in 25 ml of dimethylformamide was added drops wise and the solution refluxed 5 hours. The material - was partitioned between 500 ml of ethyl acetate and 500 ml of. water. The ethyl acetate was extracted with dilute hydrochloric acid, the acid basified with dilute sodium hydroxide and extracted with ethyl acetate. The organic layer was dried, concentrated, and the residue crystallized twice from isopropyl ether-ethyl acetate. Yield of product was 12.5 g (42%), m.p. 120.5-1 Analysis: Calculated for C18H20N2O2: C,72.95; H,6.80; N,9.46 Found : C,73.23; H,6.78; N,9.56 Preparation 2 2-(1-Methyl-3-pyrrolidinyloxy)benzamide To 85.6 g (2.2 moles) of sodium amide in 1.5 litre of dry toluene was added 202 g (? moles) of 1-methyl-3- pyrrolidinol so as not to exceed a temperature of 50 C. The mixture was then heated to 70 C. for 4.5 hours. The. mixture was cooled and 381 g (2 moles) of o-toluenesulphonylchloride was added at a rapid drop while maintaining a temperature of 20-30 C. with an ice bath. The mixture was stirred at room temperature for 2.5 hours and washed with water. The toluene solution was dried with sodium sulphate! and concentrated. The residue, dissolved in 500 ml of dimethylformamide, was added to a reaction mixture prepared by adding 119 g (2.2 moles) of sodium methoxide and 274 g (2.0 moles) of salicylamide to one litre. of dimethylfor'mamide and the mixture was worked up as in preparation 1. Yield of product was 170 g (38 , m.p. 116-1180C. Analysis: Calculated for C12H18N2O2: C,65.43; $H,7.32; N,12.72 Found : C,65.28; H,7.28 N,12.77. Preparation 3 2-[3-(1-Benzyl)pyrrolidinyloxy]benzoic acid. To a solution of 20.3 g (0.52 mole) of sodium hydroxide in 600 ml of ethanol and 400 ml of water was added 150 g (0.51 mole) of 2-[3-(1-benzyl)pyrrolidinyloxy] benzamide and the mixture was stirred at reflux for 48 hours. The mixture was concentrated on the rotary, evaporator to one-half volume and the residue was extracted with ethyl acetate to remove unreacted amide. The water layer was filtered and the pH of the filtrate adjusted to 6.5 with hydrochloric acid. The filtrate was concentrated on the rotary evaporator. The residue was dissolved in isopropyl alcohol. The resulting mixture was filtered and the filtrate concentrated. The residue 85.7 g was comprised substantially of the title compound. Preparation 4 3-[(1-Methyl-3-pyrrolidinyl)oxy]-2-naphthalenecarboxamide. To a cooled solution of 68 g (0.67 mole) of l-methyl3-pyrrolidinol and 74 g (0.73 mole) triethylamine in 700 ml of dry benzene was added dropwise 74 g (0.63 mole) of methane sulphonyl chloride. After stirring at room temperature for 45 min, the mixture was filtered and the filtrate concentrated under reduced pressure and dissolved in 100 ml of dimethylformamide. To a cooled suspension of 10.8 g (0.45 mole) of sodium hydride in 75 ml of dimethylformamide in another vessel, 84 g (0.45 mole) of 3-hydroxy-2-naphthalene carboxamide dissolved in 400 ml of dimethylformamide was added dropwise. The above prepared sulphonate solution was added dropwise and the reaction mixture stirred and heated at reflux for 16 hr. The cooled solution was diluted with 1000 ml of water and extracted twice with 500 ml portions of chloroform, The chloroform was washed with water and extracted twice with 500 ml portions of 3N hydrochloric acid. The aqueous extracts were made alkaline with 50% sodium hydroxide and extracted thrice with 500 mi portions of chloroform. After drying over magnesium su1iate, the chloroform was evaporated under reduced pressure affording 27.4 g (22%) of a pale yellow solid. Recrystallized from ethyl acetate, m.p. = 128-130 C. Analysis: Calculated for C18H18N2O2 : C,71.09; H,6.71; N,10.36 Found : C,70.88; H,6.68; N,10.37 Preparation 5 3-[(1-Methyl-3-pyrrolidinyl)oxy]-2-naphthalenecarboxylic acid oxalate [2:1]. To a solution of 21.6 g (0.54 mole) of sodium hydroxide in 500 ml of water was added 74 g (0.27 mole) of 3-[1-methyl-3-pyrrolinyl)oxy]-2-naphthalenecarboxamide. The solution was heated at reflux for 16 hrs and on cooling, the pH was adjusted to 6.8 with concentrated hydrochloric ¯ acid. The resultant solid was separated by filtration and the pE of the filtrate was adjusted to 6.02. The filtrate was concentra-ted under reduced pressure and the residue boiled in200 ml of isopropyl alcohol and filtered. The filtrate was again concentrated under reduced pressure to give 69 g (94%) of an amorphous solid. An aliquot was dissolved in isopropanol and treated with oxalic acid. The oxalate salt' was recrystallized from ethanol/water, m.p. 209-212 C. Analysis: Calculated for C17H18NO5: C,64.55; H,5.74; N,4.43 Found : C,63.86; H,5.68; N, .37 Preparation 6 Sodium 2-[(1-methyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate. To a stirred suspension of 6.4 g (0.13 mole) of 50% sodium hydride (mineral oil) in 50 ml of dimethyl sulphoxide was added dropwise 6.4 g (0.063 mole) of l-methyl-3-pyrrolidinol. During addition, the temperature rose from 25 C. to 31 C. After 10 minutes, a solution of 10 g (0.063 mole) of 2-chloronicotinic acid in 50 ml of dimethylsulphoxide was added dropwise causing the temperature to rise. When the temperature reached 55 C., it was maintained there by the intermittent use of ar ice bath until addition was complete. The mixture was then heated to 55-600C. for 1.5 hr., cooled and- filtered. The filter cake was suspended in 100 ml of ethyl acetate and filtered. The solid was recrystallized from ethyl acetatemethanol. Yield of product was 5 g., dec. 2400C. The NMR analysis .showed that the compound contained 1/3 mole of sodium acetate as impurity. Analysis: Calculated for C11H1@N2O3Na.1/3C2H3O2Na: C,51.62; H,5.20; N,10.32 Found : C,51.81; E,5.15; N,lO.39 Preparation 7 4-Chloro-2-[(1-methyl-3-pyrroldinyl)oxy]benzamide. To a solution of 55.5 g (0.55 mole) of triethylamine in 500 ml of dry benzene was added dropwise 50.5 g [0.50 mole) of l-methyl-3-pyrrolidinol at such a rate as to 0 maintain a temperature of 25-55 C. To the mixture, maintained at 20-500C., was added dropwise, 57 g (0.50 mole) of methanesulphonyl 'chloride. After stirring for I hr at room temperature, the mixture was filtered and the precipitate washed with 250 ml of hot benzene. The filtrate and wash were combined and concentrated under reduced pressure and the residue dissolved in 200 ml dimethylformamide. To a cooled suspension of 19.6 g (0.41 mole) of sodium. hydride in 100 ml of dimethylformamide in another vessel was added dropwise a solution of 70 g (0.81 mole) of 4-chlorosalicylamide in 200 ml dimethylformamide at a rate such as to maintain a temperature of 200C. To the resulting reaction mixture was added dropwise the aboveprepared sulphonate salt and the mixture was heated at reflux for 19 hrs. The reaction mixture was cooled and diluted with one liter of water. The diluted mixture was extracted three times with 300 ml portions of chloroform. The chloroform extracts were combined and extracted with two 500 ml portions of )N hydrochloric acid. The combined aqueous extract was made alkaline with 50% sodium hydroxide and extracted three times with 500 ml portions of ethyl acetate. The combined ethyl, acetate extract was dries over magnesium sulphate and concentrated under reduced pressure to give 46.5 g (45%) beige solid. The solid was recrystallized from ethyl acetate, m.p. 122-1230c. Analysis: Calculated for C12H15N2ClO2 : C,56.58; H,5.94; N, 10.99 Found : C,56.48; H,5.96; N,l0.84 Preparation 8 5-Bromo-2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide. To a cooled solution of 101 g (1.0 mole) l-methyl-3pyrrolidinol, 111 g (1.1 mole) triethylamine in 1000 ml of dry benzene was added dropwise 114 g (1.0 mole) of methanesulphonyl chloride. The reaction mixture was stirred at room temperature for 1 hour and filtered. The filtrate was concentrated under reduced pressure and dissolved in 100 ml. dimethylformamide. To a cooled suspension of 30 g (0.63 mole) sodium hydride in 100 ml dimethylformamide in another vessel was added dropwise 5-bromosalicylamide (137 g, 0.63 mole) dissolved in 750 ml of dimethylformamide. The above preparedsulphonate was added dropwise and the reaction mixture heated at reflux for 18 hrs. The cooled solution was diluted with 1000 ml of water and extracted thrice with 500 'ml portions of chloroform. The chloroform extracts were washed with water and extracted four times with 500 ml portions of 3N hydxochloric acid. The aqueous layer was made alkaline with 50k sodium hydroxide and extracted with chloroform. The chloroform extracts were washed with water,.dried over magnesium SulDhate. and evaporated under reduced pressure to give 52 g (28%) of a yellow solid. The solid was recrystallized from ethyl acetate/chloroform, m.p. 160-162 C. Analysis: Calculated for C12H15N2BrO2 : C,48.18; N,5.05; N,9.36 Found : C,48.02; H,5.01; N9.22 Preparation 9 5-Chloro-2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide bemihydrate. To a cooled suspension of 2.4 g (0.41 mole) sodium hydride in 50 ml of dimethylformamide was added dropwise 17 g (0.1 mole) of 5-chlorosalicylamide dissolved in 50 ml of dimethylformamide at a rate such that the temperature did not exceed 20 C. After addition of the salicylamide was complete, 16.7 g (0.1 mole) of romo-l-methyl- pyrrolidine dissolved in 50 ml of dimethylformamide was added dropwise. The reaction mixture was stirred and heated at reflux for 19 hr. The cooled solution was diluted with 250 ml of water and extracted twice with 250 ml portions of chloroform. The chloroform was extracted thrice with 500 ml portions of 3N hydrochloric acid. The aqueous extracts were made alkaline with 50% sodium hydroxide and extracted with ethyl acetate. Drying ovex magnesium sulphate and evaporation of the ethyl acetate under reduced pressure gave 6 g (23%) of product as a beige solid. The solid was recrystallized from ethyl acetate, m.p. 126-1280C. Analysis: Calculated for C24H32N4Cl2O5: C,54.65; H,6.11; N,10.62 Found : C,54.87; H,6.12; N,10.69 Preparation 10 1-[(1-Methyl-3-pyrrolidinyl)oxy]naphthalenecarboxamide. A solution of 118 g (0.63 mole) of l-hydroxy-2- naphthalenecarboxamide in 250 ml of dimethylsulphoxide was added dropwise to a suspension of 27.6 g (0.69 mole) of 50% sodium hydride (mineral oil) in 250 ml of dimethyl sulphoxide The reaction was exothermic and the temperature rose to 60 C In another vessel, 79 g (0.69 mole) of methanesulphonylchloride .'was added dropwise to a solution of 69.7 g (0.69 mole) of l-methyl-3-pyrrolidinol and 77 g (0.76 mole) of triethylamine in 500 ml of dry benzene while cooling with an ice bath. The mixture was stirred 15 minutes and filtered. The filter cake was washed with 500 ml of benzene and the benzene filtrates were combined and concentrated on the rotary evaporato} to about 200 ml. The residue was added dropwise to the above prepared dimethylsulphoxide solution containing the sodium salt of1-hydroxy-2-naphthalenecarboxamide while stirring at 75 C. The temperature was maintained at 75 C. for 18 with external heat. The resulting solution was cooled and an equal volume of water was' added. The mixture was extracted with three portions of chloroform. The washes were combined and concentrated. The residue was partitioned between 'ethyl' acetate and dilute hydrochloric acid. The 'acid layer was made basic with sodium hydroxide and extracted twice with ethyl acetate. The ethyl acetate washes were combined, dried over sodium sulphate and concentrated. The residue was crystallized from ethyl acetate-isooctane. Yield of solid was 55 g (32%. A portion was recrystallized twice from ethyl acetate-isooctane, m.p. 122-129 C. Analysis: Calculated for C16H18N2O2: C,71.11; H,6.71; N,l0.36 Found : C,70.96; H,6.71; N,l0.31 Preparation 11 5-Methoxy-2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide. To a solution of 151 g (1.5 mole) methyl pyrrolidinol and 166 g (1.6 mole) triethylamine in 1500'ml of dry benzene was added dropwise 171.g (1.5 mole) of methanesulphonyl chloride with cooling. The reaction mixture was stirred at room temperature for one hour and filtered. The filtrate was concentrated under reduced pressure to give an orange-coloured oil. In another vessel, to a suspension of 50% sodium hydride/ mineral oil (72 g; 1.5 mole) in 150 ml dimethylforznamide the suphonate prepared above and 139 g (0.93 mole) of 5-methoxy salicylamide dissolved in 600 ml dimethylformamide were added dropwise with cooling. The reaction mixture was heated at reflux for 14 hr. After cooling, the reaction was diluted with 1000 ml of water and extracted three times with 700 ml portions of chloroform. The combined chloroform extracts were washed thrice with water and extracted thrice with 500 ml portions of 3N hydrochloric acid. The aqueous layer was made alkaline and extracted with chloroform. The chloroform extracts were washed thrice with water, dried over magnesium sulphate and evaporated under reduced pressure to give a viscous brown oil. Vacuum distillation of this material yielded a viscous orange oil which was dissolved in chloroform, extracted in acid; made alkaline and extracted into chloroform again. Evaporation of the solvent gave a dark brown oil which solidified under reduced pressure. Three recrystallizations from ethyl acetate gave, 10 g of white, crystals (4%), m.p. 85-8"0C. Analysis: Calculated for C13H18N2O3: C,62.38; H,7.25; N,11.19 Found : C,62.47; H,7.26; N,11.20 Preparation 12 3-[(1-Methyl-3-pyrrolidinyl)oxy]-4-pyridinecarbonitrile fumarate [1:2]. A solution of 55 g (0.55 mole) of l-methyl-3 pyrrolidinol in 55 ml of dry dimethylformamide was added dropwise to a suspension of 2? g (o.58 mole) of 60% sodium hydride/40% mineral oil in 300 ml of dimethylformamide. The mixture was stirred at room temperature for one hour and 73 g (0.55 mole) of 3-chloro-4-cyano pyridine in 200 ml of dimethylformamide was added dropwise with mild cooling to maintain a temperature of 30-400C. The solution was stirred 3 hours and an equal volume of water added. The solution was made acidic with dilute hydrochloric acid and extracted with isopropyl ether. The aqueous layer was made basic with sodium hydroxide and extracted 5 times with chloroform, The extracts were combined,, dried over sodium sulphate and concentrated. The residue was treated with 50 g of fumaric acid in' 400 ml of isopropyl alcohol and 40 ml of water. The resulting crystals (51 g; 21%) were- collected. A 2 g sample was recrystallized from methyl isobutyl ketone. Yield of product was 1.5 g, m.p. 172-174 C. Analysis: Calculated for C18H21N3O9 : C,52.42; H,4.86; N,9.65 Found : C,52.40; H,4.90; N,9.68 Preparation 13 1-[(1-Methyl-3-pyrrolidinyl)oxy]-2-naphthalene carbonitrile oxalate. A solution of 29 g (0.11 mole) of 1-[(1-methyl- pyrrolidinyl)oxy-2-naphthalenecarboxamide and 38 g (-0.52 mole) of thionyl chloride in 150 ml of chloroform was heated to reflux for 6 hr. The solution was poured into ice and made basic with sodium hydroxide. The chloroform layer was separated, dried over sodium sulphate and concentrated. The residue was dissolved in hot isooctane. The solution was treated with charcoal, filtered and concentrated. The residue was dissolved in isopropyl alcohol and oxalic acid was added. The precipitate was recrystailized from isopropyl alcohol-water mixture. Yield of product was ll.5 g (31%), m.p. 176-184 C. Analysis: Calculated for C18H18N2O5: C,63.15; H,5.30; N,8.18 Found : C,63.00; H,5.29; N,8.15 3,5-Diiodo-methylsalycilate. To one liter of absolute methanol was added 150 g (0.39 mole) of 3,5-diiodosal icylic acid. Eydrogen chloride was bubbled through the reaction mixture under agitation and refluxed for 3 hrs. The reaction mixture turned cloudy and suddenly a large volume of white crystals precipitated. The mixture was filtered to give, after drying, 136'g (830 of, product, m.p. 198-202 C. Preparation 15 2-Hydroxy-3,5-diiodobenzamide. A stainless steel bomb, cooled with dry ice acetone, was charged with excess liquid ammonia, 3,5-diiodomethylsalicylate and a catalytic amount of sodium hydride. The bomb was sealed and shaken at room temperature for 16 hrs. On cooling again, the contents of the bomb were poured out and excess ammonia allowed to evaporate at room temperature. The product melted 190-195 C. with decomposition. Mass spec analysis confirmed molecular weight of . the title compound. Preparation 16 3,5-Diiodo-2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide. Following the procedure of preparation 2, substituting 2-hydroxy-3,5-diiodobenzamide for sacicylamide, the title compound is prepared. Preparation 17 Sodium-2-[(1-methyl-3-azetidinyl)oxy]-3-pyridine carboxylate. The title compound is prepared by following the procedure of preparation 6 but substituting l-methyl-3 azetidinol for 1-methyl-3-pyrrolidinol. Preparation 18 4-[(1-Methyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylic acid sodium salt. 4-Chloropyridine is reacted with diisopropyl lithium amide and carbon dioxide to, give the lithium salt of 3-carboxy-4-chloropyridine which is then reacted with l-methyl-3-pyrrolidinol as in Preparation 6. Preparation 19 3-[(1-Methyl-3-pyrrolidinyl)oxy]-2-pyridinecarbonitrile fumarate. 2 -Carboxamido -3-hydroxypyr idine is reacted with EMI44.1 to give 2-cyano-3-chloropyridine which is then reacted with l-methyl-3-pyrrolidinol as in preparation 12 to give the title compound. Preparation 20 l-MethyI-pyrro1idinethiol acetate fester) ethane- dioate. TO a solution of 101 g (l mole) of l-methyl-5- pyrrolidinol and 110 g (1.1 mole) of triethylamine in 700 ml of dry benzene was added dropwise 115 g (1 mole) of methanesulphonyl chloride while stirring and cooling with an ice bath. The resulting mixture was stirred for 0.5 hr. and filtered. The filtrate 'was concentrated on the rotary evaporator to about 200 ml being careful not to overheat. The residue was dissolved in about 150 ml of ethanol. In a separate vessel, 25.3 g (1.1 mole) of sodium was dissolved in 800 ml of 200 proof ethanol under nitrogen gas sweep. After dissolution was complete, 83.6 g (1.1 mole) of thiolacetic acid was added slowly and the resulting solution was stirred an additional 10 min; The above prepared ethanolic solution of methanesulphonate was added and the resulting solution was heated to 60 C. for 20 hrs. The mixture was cooled to 250C. and filtered and the filtrate was concentrated on a rotary evaporator. The residue was dissolved in isopropyl ether and the mixture filtered to remove a small amount of solid. The filtrate was concentrated and the residue distilled to yield 70 g of the free base title ester, b.p. 95-105/15 mm. A 7 g portion of the free base was treated with 4 g of oxalic acid in isopropyl alcohol and the salt obtained was recrystallized from isopropyl alcohol to give 8.4 g of title product, m.p. 108-111 c. Preparation 21 l-Methvl-3-pvrrolidinethiol oxalate. A solution of 62 g (0.39 mole) of l-methyl-3 pyrrolidinethiol acetate (ester) in 200 ml of absolute methanol was treated with a 2 mm sphere of sodium and the resulting solution was distilled at 1 atm. pressure to a pot temperature of 100 C. Vacuum was applied and the pressure was slowly decreased to 100 mm. The residue was distilled to a pot temperature of 30 C., yielding 25 g (56%) of distillate with a boiling point of 95-1000C./ 100 mm which was the free base of the title compound. A 4 g sample was treated with oxalic and in isopropyl alcohol to give 5.5 g of oxalate salt, m.p. 80-82 C. Preparation 22 2-[(1-Methyl-3-pyrrolidinyl)thio]-3-pyridinecarboxylic acid. To a stirred suspension of 80 g (2 mole) of 60% sodium hydride (in mineral oil) in 8Do ml of dry dimethylformamide, all heated to 60 C. and using nitrogen gas flow was added dropwise, a solution of 157.0 g ( 1 mole) of 2-chloronicotinic acid and 117 g ( 1 mole) of l-methyl-3 pyrrolidinethiol in 300 ml of dimethylformamide at a rate which maintained a temperature of 60-670c. The mixture was heated to 650c. for 6 hr and allowed to stand overnight at room temperature and then filtered. The collected solid was suspended in one litre; of isopropyl alcohol and hydrogen chloride was bubbled into the suspension until a pE of 6.2 was reached. The mixture was brought to a boil and filtered. The solid was dissolved in 2 likes of water and extracted with-isopropyl ether. The pH was adjusted to 6.0 and the solution was concentrated to a volume of 800 ml and placed in a refrigerator. The resulting solid (85 g) collected by filtration, was a mixture consisting of about 85% of the title compound and 15% sodium chloride. A sample portion of this was crystallized once from ethanol and twice from isopropyl alcohol-water. The recrystallized product decomposed at about 225 C. Preparation 23 Sodium 2-[(1-Cyclohexyl-3-azetidinyl)oxy]-3-pyridine carboxylate. A solution of 105 g (o.68 mole) of l-cyclohexyl-3- azetidinol and 106 g (0.68 mole) of 2-chloronicotinic acid in 400 ml of dry dimethylformamide was added at a rapid - drop to 52 g (1.35 mole) of 60% sodium hydride/mineral oil suspended in 400 ml of dry dimethylformamide at 60 C. Mild exothermic reaction was noted. After stirring for 2 hr at 60 c., the mixture was filtered The filter cake was washed with ethylacetate and dried at 80 C./2 mm to give 174 g (86%) of crude title compound. Intermediate 1 2-(2-Chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)-one. To 54 g (1.35 mole) of sodium hydroxide in 800 ml of water was added 148 g (0.67 mole) of 2-[(1-methyl-3 pyrroldinyl)oxy]benzamide and the mixture broug'ht to reflux for 18 hr. The pH was adjusted to 7 with hydrochloric acid and the solution filtered and concentrated. The residue was boiled with 4pO ml of isopropanol and filtered. The filtrate was concentrated and the residue (which crystallized) was refluxed with 300 ml of thionyl chloride for 0.5 hr. and concentrated in vacuo. The residue was dissolved in 300 ml of chloroform and the solvent boiled off in vacuo. The residue was redissolved in chloroform, 150 ml of triethyl amine added and the mixture refluxed 1 hr. The solution was concentrated in vacuo and the residue partitioned between 400 ml of ethyl acetate, 400 ml of isopropyl ether and 500 ml of dilute hydrochloric acid. The organic layer was washed twice with water and once with dilute sodium hydroxide, dried with sodium sulphate and concentrated. The residue was crystallized from isopropanol-water. Yield of product was 75 g (47%), m.p. 97-107 C. Analysis: Calculated for C12H14NO2Cl: C,60.13; H,5.89; N,5.84 Found : C,60.35; H,5.91; N,5.65 - Intermediate 2 4-Benzyl-2-(2-chloroethyl)-2,3-dihydro-1,4-benzoxazepin-5(4H)-one. To 85.7 g (0.29 mole) of 2-[(1-benzyl-3-pyrrolidinyl) oxy]-benzoic acid was added 150 ml of thionyl@ chloride. The solution stood for 15 min and was then refluxed 30 min. and concentrated in vacuo. The residue was twice treated with 250 ml, of chloroform and concentrated in vacuo. The residue was dissolved in 500 ml of chloroform and 101 g (1 mole) of triethylanine added slowly with stirring. The solution was refluxed 1 hr. and concentrated in vacuo. The residue was partitioned between 50% ethyl acetate- O% isopropyl ether and dilute 'hydrochloric acid. The organic layer was washed with dilute sodium hydroxide and concentrated. The residue was crystallized 5 times from isopropyl ether-ethyl acetate. Yield of product was 23.8 g (26%), m.p. 145.0-1470C. Analysis: Calculated for C18H1#NO2Cl: C,68.46; N,@@@@ Found : C,68.47; N,5.89; N,4.32 Intermediate 3 2-(2-(Chloroethyl)-2,3-dihydro-4-methylnaphth[2,3-f] [1,4]oxazepin-5-(4H)-one. To a solution of 21.6 g (0.54 mole) sodium hydroxide in 500 mi of water was added 14 g (0.27 mole) of 3 [1-methyl-3-pyrrolidinyl)oxy]-2-naphthalenecarboxamide and the mixture heated at reflux for 16 hr. The pH was adjusted to 6.8 with concentrated hydrochloric acid; the solution was filtered and concentrated. The residue was boiled with 200 ml of isopropyl alcohol and filtered. The filtrate was concentrated under reduced pressure and the residue dissolved in chloroforo. Thionyl chloride (59 g, 0.50 mole) was added and the reaction mixture heated at reflux for 4 hr. After cooling (67 g, 0.67 mole) triethylamine was added dropwise. The mixture was washed sequentially; twice with 3N hydrochloric acid, twice with water, twice with 10% sodium hydroxide, twice with water and dried over magnesium nulphate. Evaporation of the chloroform under reduced pressure gave 44 g of'a viscous dark brown oil. The material was purified by high pressure liquid chromatography (50/50 ethyl acetate/ hexane) and recrystallized from isopropyl alcohol to yield brown crystals, m.p. = 101-1020C. Analysis: Calculated for C16H16NClO2: C,66.32; H,5.57 N,4.83 Found : C,66.19; H,5.63; N,4.77 Intermedlate 4 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]-oxazepin-5(4H)-jone hydrochloride. Hydrogen choride gas was bubbled into a suspension of 150 g (0.61 mole) of sodium 2-[(1-methyl)-3-pyrrolidinyl) oxy)-3-pyridinecarboxylate in 1 litre of chloroform until a pE of 6 was reached. To the stirred mixture was added 350 g (1.34 mole) of triphenylphosphine and 350 g (2.3 mole) of carbon tetrachloride,and the resulting cloudy solution was stirred at reflux for 1.5 hr. About 100 ml of ethanol was added and the heat removed. The solution was stirred for 1 hour while cooling and 200 ml of isooctane was added. The solution was extracted 4 times with a total of 800 ml of dilute hydrochloric acid, The acid extracts were combined, made basic with sodium hydroxide and extracted with chloroform. The chloroform layer was separated and dried over sodiumsulphate and concentrated. The residue was dissolved in a mixture of 500 ml each of isopropyl alcohol and isopropyl ether and acidified with ethereal hydrogen chloride. The resulting crystals weighed 82 g (49%). A portion was recrystallized from isopropyl alcohol, m.p. 149-153 C. Analysis: Calculated for C11H14N2O2Cl2l: C,47.67; H,5.09; N,10.11 Found : C,47.57; H,5.18; N,10.00 Intermediate 5 8-Chloro-2 -(2 -chloroethyl) -2, dihydro-4 -methyl-l 4- benzoxazepin-5(4H)-one. To a solution of 10.4 g (0.26 mole) of sodium hydroxide in 150 ml of water was added 32 g (0.13 mole) of 4-chloro2-[(1-methyl-3-pyrrolinyl)oxy]benzamide and the mixture was heated at reflux for 24 hr. The reaction mixture was adjusted to pH 6 with concentrated hydrochloric acid and filtered and the filtrate concentrated. The residue was boiled with 100 ml of isopropyl alcohol and the mixture filtered. The filtrate was concentrated and heated at reflux with 98 g (o.8) mole) of thionyl chloride for 1 hr. The excess thionyl chloride was evaporated under reduced pressure. The residue was dissolved-in 70 ml of dhloro form and the solvent evaporated under reduced pressure. The residue was redissolved in 75 ml of chloroform and 40 ml of triethylamine was added gradually. The mixture was heated at reflux for 1 hr. The solvent was evaporated under reduced pressure to give a d,ark-brown solid. The solid was dissolved in ethyl acetate and the resulting solution washed twice with 200 ml of water and twice with 250 ml of 20,g sodium hydroxide. The organic layer was dried over magnesium sulphate and concentrated under reduced pressure to give 21 g (59%) of dark-brown solid. The solid was recrystallized from isopropyl alcohol to give the title compound, m.p. 85-870C. Analysis: Calculated for C12H13NCl2O2: C,52.57; H,4.78; N,5.11 Found : C,52.57; H,4.77; N,5.O-11 Intermediate 6, 7-Bromo-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4 benzoxazepin-5(4H)-one. To a solution of 9.6 g (0.24 mole) of sodium hydroxide in 200 ml of water was added 37 g (0.12 mole) of 5-bromo 2-( (1-methyl-3-pyrrolidinyl)oxy]-benazmide and the mixture was heated at reflux for 18 hr. The pE of the mixture was adjusted to 6.7 with concentrated hydrochloric acid solution. The solution was concentrated under reduced pressure and the residue was boiled in 250 ml of isopropyl alcohol for 1 hr. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in chloroform and to the solution was added 28.3 g (0.28 mole) of thionyl chloride. The mixture was heated at reflux for 0.5 hr and cooled to 15 C. with an ice bath. To the mixture was added dropwise 26.6 g (0.26 mole) of triethyl amine at such a rate that the temperature did not exceed 250C. The reaction mixture was stirred at room temperature for 1 hr, then washed consecutively with 3N hydrochloric acid, 15% aqueous sodium hydroxide and water. The chloroform layer was dried over magnesium sulphate, and concentrated under reduced pressure to give 23 g (60%) of brown solid. 'A portion of the solid was recrystallized from ethyl acetate-isopropyl ether, m.p. 92-940c. Analysis: Calculated for C12H13NBrClO2: C,45.24; H,4.ll N,4.40 Found : C,45.61; H,4.17; N,4.42 . Intermediate 7 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4benzoxazepin-5(4H)-one. Hydrogen chloride was bubbled through a solution of 113 g (0.44 mole) 5-chloro-2-[(1-methyl-3-pyrrolidinyl)oxy] benzamide dissolved in 500 ml of glacial acetic acid for 15 min while the reaction was cooled with an ice bath. Butylnitrite (142 g, 1.38 mole) was then added in one portion; the reaction was stirred at room temperature for 16 hr and heated at reflux for an additional 6 hr. 'The acetic acid was evaporated under reduced pressure, tetrachloroethane was added twice to the residue and evaporated. The residue was dissolved in chloroform, treated with 163 g (1.38 mole) of thionyl chloride and heated at reflux for 22 hr. The reaction mixture was cooled with an ice bath and 152 g (1.5 mole of triethylamine was added dropwise at such a rate that the temperature was kept at 25-30 C. The reaction mixture was diluted with 200 ml of chloroform and washed consecutively with 3N hydrochloric acid, water, 10% sodium hydroxide and water. The chloroform was evaporated under reduced pressure to give 40 g of a black, tar-like residue (33%). An aliquot of this residue was purified on a silica gel column using ethyl acetate as the eluting solvent. Recrys'tallization from isopropyl alcohol gave beige crystals, m.p. 101-103 C. Analysis: Calculated for C12H13NCl2O2: C,52.57; H,4.78; N, .11 Found : C,52.63; H,4.83; N,5.05 Intermediate 8 2-[(2-chloroethyl)-2,3-dihydro-4-methylnaphth[2,1-f] [1,4]oxazepin-5(4H)-one. Hydrogen chloride gas was bubbled into a solution of 8 g (0.03 mole) of 1-[(1-methyl-3-pyrrolidinyl)oxy]-2 naphthalenecarboxamide in 40 ml of acetic acid for about 2 min. The solution was cooled with an ice bath and 6.t g (0.06 mole) of n-butyl nitrite was added slowly beneath the surface of the liquid at 12-150C. (about 10 minutes required). The solution was stirred at 25 C. for 18 hr and heated on the steam bath for 3 hr. The solution was concentrated on the rotary evaporator., The residue was dissolvec in 60 ml of 1,1,2,3-tetrachloroethane which was removed on the rotary evaporator at 0.5 mm/steam tempera ture. The residue was dissolved in 75 il of chloroform and treated With 7 g (0.06 mole) of thionyl chloride ,and # brought to reflux for 12 hr. The solution was extracted with water (tested acidic) followed by dilute sodium hydroxide, dried over sodium suphate and concentrated. The residue.was crystallized twice from isopropyl, ether- ethyl acetate. Yield of product w,as 3.2 g (37%), m.p. 109-111 C. Analysis: Calculated for C16H13NO2Cl: C,66.32; H,5.57; N,4.84 Found : C,66.15; H,5.56; N,4.76 Intermediate 9 2-(2-chloroethyl)-2,3-dihydro-7-methoxy-4-methyl-1,4benzoxazepin-5(4H)-one. To a solution of 19.2 g (o.48 mole) of sodium hydroxide in 500 ml of water was added 60 g (0.24 mole) of 5-methoxy- 2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide and the mixture was heated at reflux for 24 hr. The reaction mixture was cooled and the PH adjusted to 6.8 with concentrated hydrochloric acid. The mixture was concentrated under reduced pressure and the residue was boiled in isopropyl alcohol for 1 hour. The mixture was filtered and the filtrate was concentrated. The residue was dissolved in 500 ml of chloroform and to this solution was added 114 g (o.g6 mole) of thionyl chloride. The mixture was heated at reflux for 48 hr, then cooled with an ice/acetone bath. To the mixture was added dropwise 97 g (0.96 mole) of triethylamine at such a rate that the temperature did not exceed 25 C. The reaction solution was washed in sequence with water, 3N hydrochloric acid solution, water, 15% aqueous sodium hydroxide and water and finally dried over magnesium sulphate The solvent was evaporated under reduced pressure to give a black solid. The solid was purified on a silica gel column using ethyl acetate as the eluting solvent to give on isolation' 15 g (23%) of beige colored product, m.p. 98-1000c. Analysis: Calculated for C15H16NClO3: C,57.89; H,5.98; N,5.19 Found : C,57.53; H,6.00; N,5.16 Intermediate 10 2-(2-Chloroethyl)-2,3-dihydro-4-methyl-1,4-benzox azepine-5 ( 4H) -thione. A mixture of 18.5 g (o.o834 mole) of phosphorus pentasulphide and 18.5 g potassium sulphide was ground together and added to a solution of 100 g (0.1117 mole) of 2-(2-chlorethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin5(4H)-one in dry toluene, the mixture refluxed 24 hr. and filtered. The filtrate was concentrated and partitioned between chloroform and dilute sodium hydroxide. The chloroform layer was concentrated and the residue'was crystallized several times from ethanol. Yield of product was 55 g (52%), m.p. 105-1080C. Analusis: Calculated for C12H14NSOCl: C,56.35; H,5.52; N,5.48; S,12.54 Found : C,56.55; H,5.47; N,5.49; S,12.55 Intermediate lr 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]-oxazepine-5(4H)-thione. TO a solution of 59 g (0.25 mole) of 2-(2-chloroethyl) 2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)one hydrochloride in 1500 ml of chloroform was added,41.5 g (0.19 mole) of phosphorus pentasulphide and the mixture was heated to reflux for 18 hr. The mixture was filtered and the filtrate was extracted With dilute sodium hydroxide. The chloroform layer was concentrated and the residue was dissolved in 250 ml of boiling isopropyl alcohol. On cooling, 28 g (44%) of yellow solid precipitated. A portion was recrystallized from isopropyl alcohol, m.p. 134-136 C. Analysis: Calculated for C11H13N2ClOS: C,51.46; H,5.10; N,10.81 Found : C,51.35; H,5.21@ N,10.72 Intermediate 12-- 2-(2-Chloroethyl)-2,3-dihydro-4-methylnaphth[2,3-f [1,4]oxazepine-5(4H)-thione. To a solution of 16.6 g (O..o6 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylnaphth[2,3-f][1,4]oxazepin5(4H)-one in 150 ml of dry toluene was added a mixture of 8.6 g (0.045 mole) of phosphorus pentasulphide and 8.6 g of potassium sulphide which had been ground together. The reaction mixture was stirred and heated at reflux for ?4 hr. The mixture was filtered hot and the filtrate concentrated under reduced pressure. Yellow solid, 6.5 g (35%) was obtained which was recrystallized from ethanol, m.p. 166-i68 C. Analysis: Calculated for C1@H1@NClOS: C,62.84; H,5.27; N,4.58 Found : C,62.29; H,5.48; N,4.47 .Intermediate 13 8-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4benzoxazepine-5(4H)-thione. To a solution of 43 g (0.16 mole) of 8-chloro-2-(2- chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H) one in 400 ml of dry toluene was added a mixture.of 23 g (0112 mole) of phosphorus pentasulphide and 23 g of potassium sulphide which had been ground together. The reaction mixture was stirred and heated at reflux for 24 hr. The mixture was filtered hot and the filtrate concentrated under reduced pressure to give 25.5 g (55%) of orange oil which solidified on standing at room temperature. The solid was recrystallized from ethanol, m.p. 105-106 C. Analysis: Calculated for C12H1@NCl2OS: C,49.66; H,4.52; N,4.83 Found : C,49.63; H,4.53; N,4 -75 Intermediate 14 7-Bromo-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4 benzoxazepine-5(4H)-thione. To a solution of 11.0 g (O.Q35 mole) of 7-bromo-2 (2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H one in 150 ml of dry toluene was added a mixture 6f 13.4 g (0.07 mole) of phosphorus pentasuiphide and 13.4 g of .potassium sulphate which had been ground together. The reaction mixture was heated at reflux for 5 hr under a nitrogen atmosphere. The mixture was filtered hot and the filtrate concentrated under reduced pressure. The residue was dissolved in chloroform. The chloroform solution was washed twice with dilute aqueous sodium hydroxide, dried over magnesium sulphate and concentrated under reduced pressure to give 8.5 g (72 5s) of yellow solid. The solid was recrystallized from ethanol, m.p. 118-1200c. Analysis: Calculated for C12H13NBrClOS: C,43.07; H,3.92; N,4.18 Found : C,43.08; H,3.88; N,4.12 Intermediate lS 2- (2-Chioroethyl) -2, 3-dihvdro-fi -methyln¯aphthy2 . l-f [1,4]oxazepine-5(4H)-thione. A mixture of 9.55 g of phosphorus pentasulphide and 9.5 g of potassium sulphite were ground together and added to a solution of 20.2 g (0.07 mole) of 2-(2-chloroethyl)- 2,3-dihydro-4-methylnaphth[2,1-f][1,4]oxazepin-5(4H)-one in 200 ml of dry toluene. The mixture was stirred and heated at reflux for 7 hr. The hot reaction mixture was filtered and the product crystallized from the cooled filtrate. Recrystallization from chloroform gave 18 g (84%) of yellow crystals, m.p. l67-1700C. Analysis: Calculated for C1@H1@NClOS: C,62.84; H,5.27; N,4.58 Found : C,62.84; H,5.20; N,4.55 Intermediate 16 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[4,3-f] [1,4]-oxazepin-5(4H)-one hydrochloride. A 49 g (0.11 mole) sample of 3-[(1-methyl-3- pyrrolidinyl)oxy]-4-pyridinecarbonitrile fumarate [1:2] was partitioned between chloroform and a saturated solution of potassium carbonate. The aqueous layer was extracted twice with chloroform. All chloroform extracts were combined, dried and concentrated. The residue was dissolved in 125 ml of t-butanol and added to 34 g (0.6 mole) of potassium hydroxide pellets., The mixture was stirred at room temperature for 88 hr. and then diluted with 150 ml of toluene. This mixture was filtered and the filtrate concentrated. The residue was dissolved in chloroform, with cooling, and the pE adjusted to 6.o with hydrogen chloride gas. The resulting mixture was concentrated and 400 ml of dry toluene was added to the residue. The toluene was removed on the rotary evaporator (steam heat/reduced pressure) to remove any water. The residue was dissolved in 400 ml of chloroform and 63 g of triphenylphosphine was added followed by 70 g of carbon tetrachloride. The solution was stirred at reflux for 2 hr and another 30 g of triphenylphosphine added. After an additional hour reflux, 70 g more carbon tetrachloride and 63 g more of triphenylphosphine were added and reflux was continued. for 4 hr. The solution was extracted with dilute sodium hydroxide, then concentrated. The residue was partitioned between toluene and dilute hydrochloric acid. The toluene layer was extracted five times with dilute hydrochloric acid. The acid extracts were combined, basified with sodium hydroxide and extracted with chloroform. The chloroform layer was dried over sodium sulphate and concentrated. The residue was chromatographed on a 7 x 25 cm column of silica gel with acetone liquid phase. Free base of the title compound isolated after evaporation amounted to 5.8 g (20%). To a portion of the free base dissolved in isopropyl alcohol was added ethereal hydrogen chloride and isopropyl ether. The resulting crystals were collected and dried, m.p. 188-190 C. Analysis: Calculated for C11H14N2O2Cl2: C,47.67; H,5.09; N,10.11 Found - : C,48.33; H,5.22; N,9.73 Intermediate 17 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,4-f] r 1,4 )oxazepin-5( 4H) onehydrochloride. In the procedure of Intermediate 4, equal molar amounts of sodium 4[(1-methyl-3-pyrrolidinyl)oxy]-3pyridinnecarboxylates was substituted for 2-[(1-methyl-3 pyrrolidinyl)oxy]-3-pyridinecarboxylic acid and the title compound 'was obtained. Intermediate 18 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[2,3-f] [ 1, 4 Zcxxa2 epin-5 ( 4H)-one hydrochloride. When in the procedure of Intermediate 16, 3-((l-methyl- 3-pyrrolidinyl)oxy]-2-pyridinecrbonitrile fumarate is substituted for 3-[(1-methyl-3-pyrrolidinyl)oxy]-4pyridinecarbonitrile fumarate, the title compound is obtained. Intermediate 19 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4benzoxazepine-5(4H)-thione. TO a solution of 20 g (0.07 mole) of 7-chloro-2-(2- chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)one in 200 ml of toluene was added a mixture of 9.55 g (0.05 mole) of phosphorus pentasulphide. and 9.5 g of potassium sulp,,h,ide which had been ground together. The reaction mixture was filtered'and the filtrate concentrated under reduced pressure to give a yellow solid. Recrystallization from absolute ethanol gave 12.5 g (68%) of the product, m.p. 102-104 C. Analysis: Calculated for C12H1@NCl2O5: C,49.66; H,4.52; N,4.83 Found : C,49.62; H,4.55; N,4.76 Intermediate 20 2-(2-Chloroethyl)-7,9-diiodo-2,3-dihydro-4-methyl1,4-benzoxazepin-5(4H)-one. ten in the procedure of Int'ermediate 1, 3, 5-di'ido- 2-[(1-methyl-3-pyrrolidinyl)oxy]-benzamide is substituted for 2-[(1-methyl-3-pyrrolidinyl)oxy]benzamide, the title compound is prepared. Intermediate 21 2-Chloromethyl-2,3-dihydro-4-methylpyrido[3,2-f][1,4] oxazepin-5( 4R) -hydrochloride. ten in the procedure of Intermediate a, an equal molar amount of sodium 2-[(1-methyl-3-azetidinyl)oxy]-3-pyridine- carboxylate sodium acetate is substituted for sodium 2- - [(1-methyl-3-pyrrolidinyl)oxy]-3-pyridinecarboxylate, the title compound is prepared. Intermediate 22 2(2 -Chloroethyl) -2, 3-dihydro-4 -methylpyrido [4,3-f] [1,4]oxazepine-5(4H)-thione. A solution of 5 g (0.021 mole) of 2-(2- iloroethyl)- 2,3-dihydro-4-methylpyrido[4,3-f][1,4]-oxazepine-5(4H)-on and 5.1 g (o.o126 mole) of 2,4-bis(4-methoxyphenyl)-1,3,2,4- dithiodiphosphetane-2,4-disulphide in 100. ml of dry toluene was stirred at reflux for 2.5 hr. The solUtion was cooled and extracted three times with sodium bicarbonate solution. The toluene layer was dried over sodium sulphate and concentrated. - The residue was chromatographed (high pressure liquid chromatograph) using a silica column and'ethyl acetate liquid phase. The fraction containing the product was concentrate; by evaporation and the residue was crystallized from ethyl alcohol to give o.6 g (510 of the title compound. Intermediate 23 2 -(2 -Chloroeth'yl ) x, 3-dihydro-7-methoxy-4-methyl-1, 4 benzoxazepine-5(4H)-thione. To a solution of 10.3 g (004 mole) of 2-(2-chloroethyl)-2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin5(4H)-one in 200 ml of chloroform was added a mixture of 5.7 g (0.03 mole) of phosphorus pentasulphide 5.7 g of potassium sulphide which had been ground together. The-" reaction mixture was stirred and heated at reflux under nitrogen atmosphere for 5 hr. The-mixture was filtered hot and the filtrate concentrated under reduced pressure. The residue, an orange solid, was -re'crystallized from - ethanol to give 7.4 g (65%) of product, m.p. 98-100 C. Analysis: Calculated for C1@H1@NClO2S: C,56.64; H,5.65 N,4.90 Found : C,54.57; H,5.67 N,4.85 Intermediate 24 When in the procedure of Intermediate 2, equal molar amounts of the following are substituted for 2-(1-benzyl-3- pyrrolidinyloxy)benzoic acid: 2-[(1-cyclohexyl-3-pyrrolidinyl)oxy]benzoic acid, 2-E( l-ethyl-3-pyrrol iainyl) oxy)benzoic acid, 2-[(1-isopropyl-3-pyrrolidinyl)oxy]benzoic acid, 2-[[(1-(4-chlorobenzyl)-3-pyrrolidinyl]oxy]benzoic acid, 2-[[1-(4-methylbenzyl)-3-pyrrolidinyll]oxy]benzoic acid, 2-[[1-(3,5-dimethoxybenzyl)-3-pyrrolidinyl]oxy]benoic acid, 2-[[1-(3-trifluoromethylbenzyl)-3-pyrrolidinyl]oxy] benzoic acid, and 2-[[1-(4-nitrobenzyl)-3-pyrrolidinyl]oxy]benzoic acid, there are obtained: : a) 2-(2-chloroethyl)-4-cyclohexyl-2,3-dihydro-1,4 benzoxazepin-5(4H)-one, b) 2-(2-chloroethyl)-2,3-dihydro-4-ethyl-1,4-benzox azepin-5(4H)-one, c) 2-(2-chloroethyl)-2,3-dihydro-4-isopropyl-1,4 benzoxazepin-5(4H)-one, d) 2-(2-chloroethyl)-4-(4-chlorobenzyl)-2,3-dihydro 1,4-benzoxazepin-5(4H)-one, e) 2-(2-chloroethyl)-2,3-dihydro-4-(4-methylbenzyl) 1,4-benzoxazepin-5(4H)-one, f) 2-(2-chloroethyl)-2,3-dihydro-4-(3,5-dimethoxybenzyl) 1,4-benzoxazepin-5(4H)-one, g) 2-(2-chloroethyl)-2,3-dihydro-4-(3-trifluoromethyl benzyl)-1,4-benzoxazepin-5(4H)-one, h) 2-(2-chloroethyl)-2,3-dihydro-4-(4-nitrobenzyl) 1,4-benzoxazepin-5(4H)-one. Intermediate 25 hen in the procedue oS mtermediate 4, equal molar amounts of the following are substituted for sodium 2 [(1-methyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate: 2-[(1-cyclohexyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate, 2-[(1-ethyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate, 2-[1-isopropyl-3-pyrrolidinyl)oxy]-3-pyridine carboxylate, 2-[[1-(4-chlorobenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, 2-[[1-(4-methylbenzyl)-3-pyrrolidinyl]oxy]-3-pyridine carboxylate, 2-[[1-(4-methoxybenzyl)-3-pyrrolidinyl]oxy]-3 pyridine carboxyalate, 2-[[1-(3-trifluoroemethylbenzyl)-3-pyrrolidinyl]oxy] 3-pyridine carboxylate, and 2-[[1-(4-nitroenzyl)-3-pyrrolidinyl]oxy]-3-pyrridine carboxylate, there are obtained: : a) 2-(2-chloroethyl)-4-cyclohexyl-2,3-dihydro-pyrido [3,2-f][1,4]oxazepin-5(4H)-one hydrochloride, b) 2-(2-chloroethyl)-2,3-dihydro-4-ethylpyrido[3,2-f] [1,4]-oxazepin-5(4H)one hydrochloride, c) 2-(2-chloroethyl)-2,3-dihydro-4-isopropylpyrido[3,2-f] [1,4]-oxazepin-5(4H)-one hydrochloride, d) 2-(2-chloroethyl)-4-(4-chlorobenzyl)-2,3-dihydro pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, e) 2-(2-chloroethyl)-2,3-dihydro-4-(4-methylbenzyl) pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, f) 2-(2-chloroethyl)-2,3-dihydro-4-(4-methoxybenzyl) pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, g) 2-(2-chloroethyl)-2,3-dihydro-4-(3-trifluoromethyl benzyl)pyrido[3,2-f][1,4]-5(4H)-one hydrochloride, and h) 2-(2-chloroethyl)-2,3-dihydro-4-(4-nitrobenzyl) pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydro 'chloride. Intermediate 26 2(2 -Chloroethyl) -2 ,3-dihydro-4-methylpyrido[3,2-f] [1,4]-thiazepin-5(4H)-one. Admixture of 80-75 g (0.34 mole) of 2-[(1-methyl-3- pyrrolidinyl)thio]-3-pyridinecarboxylic acid, 500 ml of chloroform, 200 g of carbon tetrachloride and 178 g (0.68 mole) of triphenylphosphine was stirred at reflux for 2.5-hr. The resulting solution was extracted with one 500. ml and three 125 ml portions of 1N hydrochloric acid. The acid extracts were combined and extracted with isopropyl ether. The aqueous layer was basified with sodium hydroxide and extracted three times w,ith chloroform. The combined chloroform extract was, dried over sodium sulphate and concentrated. A portion of the residue was chromatographed on the high pressure liquid chromatograph using a silica column and ethyl acetate. The compound obtained was crystallized from isopropyl ether-isopropyl alcohol, m.p. 97-1000C. Analysis: Calculated for C11H13N2OSCl: C,51.46; H,5.10; N,10.91 Found : C,51.63; H,5.12; N,10.85 Intermediate' 27 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]-thiazepine-5(4H)-thione. A mixture of 4.3 g (0.017 mole) of 2-(2-chloroethyl)- 2,3-dihydro-4-methylpyrido[3,2-f][1,4]thiazepin-5(4H)-one, 100 ml of toluene and 4.8 g (0.012 mole) of 2,4-bisth- methoxyphenyl)-1,3,2,4-dithiaziphosphetane-2,4-disulphide was refluxed for 3 hr and then extracted 'twice with dilute sodium hydroxide. The organic layer was concentrated and the residue chro'matographed on the high pressure liquid chromatograph using a silica column and 50% ethyl acetate50% hexane. The yield of title compound was 2 g, m.p. 160-162 C. Analysis: Calculated for C11H13N2S2Cl: C,48.43; H,4.80; N,10.27 Found : C,48,46; H,4.81; N,10.51 Intermediate 28 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,4,-f] [1,4]oxazepin-5(4H)-one. A solution of 78 g (o.5 mole) of 4-chloronicotinic acid and 52 g (0.52 mole) of 1-methylpyrrolidinol in 150 ml of dimethylformamide was added to a suspension of 44 g ('1.1 mole) of 60k sodium hydride/mineral oil in 800 ml of dimethylformamide at a rate so as to maintain a temperature of 55-70 C. (preheated to 550C.). The resulting mixture was heated to 600C. for 4 hr and filtered while hot. The filtrate was concentrated on the rotary evaporator (5 mm/steam bath). The, residue was dissolved in 600 ml of water and extracted with isopropyl ether. The pH of the aqueous layer was adjusted to 6 with hydrochloric acid and the solution was concentrated on the rotary evaporator (5 mm/steam bath). The residue was suspended in 800 ml of chloroform and 188 g (1.1 mole) of triphenylphosphine added followed by 250 ml of carbon tetrachloride. The mixture was gently heated to 60 C. whereupon the reaction became exothermic and an ice bath was used to maintain a temperature of 60-655C. for about 20 minutes. The ice bath was removed and the mixture was heated to reflux for 3;5 hr and cooled. The solution was extracted with 600 ml of water followed by two 200 ml portions of IN hydrochloric acid. The acid layer was made basic with sodium hydroxide and extracted three times with chloroform. The chloroform was concentrated and the residue was chromatographed by high pressure liquid chromatograph,,y using silica gel and eluting with ethyl acetate. Yield of product was 30 g (25%). The mass spectra and NMR are inagreement with the structure of the title compound. # Intermediate 29 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,4-f][1,4] oxazepine-5(4H)-thione monohydrochloride. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,4-f] l,4)oxazepin-5(4H)-one, 15 g (o.o6 mole), was dissolved in 200 ml of dry toluene and 15 g (0.037 mole) of E2,4-bis (4-methoxyphenyl)-1,3,2,4-dithiaphosphetane -2,4-disulphide was added. The mixture was refluxed for 2.5 hr and the toluene solution decanted. The residue was partitioned between dilute sodium hydroxide and chloroform. The chloroform was dried and concentrated. The residue was chromatographed on a high pressure liquid chromatograph (Waters 500) using a silica column and eluting with ethyl acetate. The fraction containing material of molecular weight 257 was concentrated. The residue in isopropyl alcohol was treated with hydrogen chloride and the resulting crystals were collected. Yield of hydrochloride salt was 0.1 g m.p. 168-1710C. Analysis: Calculated for C11H14N2OSCl2 : C,45.06; H,4.81; N,9.55 Found : C,45.15; H,4.98; N,9.26 Intermediate 30 2,3,4,5-Tetrahydro-4-methyl-5-oxopyrido[3,2-f][1,4] oxazepine-2 -propanenitrile. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] El,4)oxazepin-5(4E)-one hydrochloride, 100 g (0.415 mole) was partitioned between dilute aqueous sodium hydroxide (200 ml) and chloroform (200 ml). The organic layer was saved and the aqueous layer extracted with chloroform (3 x 50- ml). The organic layer were combined, dried over sodium sulfa,te and concentrated by rotary evaporation (700C., water aspirator). The residue, the free base of the starting hydrochloride, 89 g (0.37 mole) was dissolved in 150 ml of toluene and to the solution was added te'trabutyl ammonium bromide, 9 g (0.027 mole). Saturated agueous potassium cyanide (100 ml) was then added and the mixture stirred mechanically at reflux. After 2.hr, additional .tetrabutyl ammonium bromide, 3 g (0.009 mole) and saturated aqueous potassium cyanide (20 ml) were added and the mixture stirred for 0.75 hr at reflux. The contents of the reaction vessel were extracted with ethyl acetate (3 X 50 m). (Note: chloroform should be used instead). The organic layer dried over sodium sulphate and concentrated by rotary evaporation (70 C., water aspirator) to 1/3 the original volume. . Upon cooling, crystallization ensued. The crystals were filtered and washed with several portions of ethyl acetate and isopropyl ether. Thirty g (35%) of off-white crystals were collected, m.p. 104-1050C. A sample was recrystallized from ethyl acetate, m.p. 104-105 C. Abalysis: Calculated for C12H15N3O2: C,62.33; H,5.67; N,18.17 Found : C,62.06; H,5.65 N,17.97 Intermediate 31 2-(2-Chloroethyl)-4-ethyl-2,3-didhydropyrido[3,2-f] [1,4]oxazepin-5(4H)-one hydrochloride, To a stirred suspension of sodium hydride mineral oil (81.45 g of 60% dispersion 2.036 mole) in dimethylsulphoxide (500 ml) heated to 500C. was added dropwise a solution of 2-chloronicotinic acid, (142 g, 0.905 mole) and N-ethyl-2-pyrrolidinol (99,g, o.86 mole) in dimethylsulphoxide (500 ml) at a rate to maintain 55 -60 C. (occasional cooling was necessary). After the addition was complete, the mixture was stirred at 5o0-600c. for 1.5 hr and allowed to cool. The solid which precipitated was filtered, washed with ethyl acetate and dried. The dry sodium salt (172.53 g, 0.62 mole) was suspended in chloroform (1 liter). Hydrogen chloride gas was bubbled through the suspension until the pE meter read', 5.76. Triphenylphosphine (365.5 g, 1.395 mole) ane CCl4 (365.5 g) were added and the mixture stirred at reflux'. After 45 minutes, IR showed 95% reaction. Additional triphenylphosphine (100 g, 0.38 mole) and CC14 (100 g) were added and the solution stirred at reflux an additional 45 min. IR showed > 99% reaction. After cooling, the solution was extracted several times with dilute. hydrochloric acid (1.5 liter total) The aqueous layer was then made basic with concentrated sodium hydroxide solution and extracted into chloroform (3 x 250 ml).- The organic layer was dried over sodium sulphate and concentrated by rotary evaporation (700C, water aspirator). The residuel oil was dissolved in isopropyl alcohol (500 ml) and acidified with hydrogen chloride gas. Upon cooling, an oil was noted and the volume reduced to 1/3 the original volume. Upon cooling, 70 g (.281 mole, 28%) of pale brown crystals were collected, m.p. 153-1550C. Analysis: Calculated for C12H1@N2O2Cl2: C,49.50; H,5.53; N,9.62 Found : C,49.64; E,5.62; N, 9.342 Intermediate 32 2-(2-Chloroethyl)-4-ethyl-2,3-dihydropyrido[3,2-f] [1,4]oxazepin-5(4H)-thione hydrochloride. 2-(2-Chloroethyl)-4-ethyl-2,3-dihydropyrido[3,2-f] [1,4]oxazepin-5(4H)-one hydrochloride, approximately 50 g, was partitioned between dilute aqueous sodium hydroxide (50 ml) and chloroform ('o ml). The organic layer was saved and the aqueous layer extracted with additional methylene chloride (2 x 50 ml). The organic layers were combined, dried over sodium sulphate, filtered and concentrated by rotary evaporation (""00C, water aspirator) yielding 39 g (0.153 mole) of the free base. The free base thus obtained was dissolved in chloroform (1.2 1), and phosphorus pentasulphide (33.9 g, 0.153 mole) was added while stirring. The resulting mixture was - heated to reflux for 16 hr. After coeling, the reaction- mixture was filtered, washed with dilute aqueous sodium hydroxide (3 x 300 ml), dried over sodium sulphate and concentrated by rotary evaporation (70 C, water aspirator) to a yellow viscous oil. The oil was taken up in isopropyl alcohol (S? ml) and made acidic with hydrogen chloride gas. Upon cooling, 20 g (43%) of crystals were collected, m.p. 133-135 C. Analysis: Calculated for C12H1@N2OSCl2: C,46.91; H,5.25; N,9.12 Found : C,47.33; H,5.38; N,9.10 Intermediate 33 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)-one. A sample of 2-(2-chloroethyl)-2,3-dihydro-4-methyl- pyrido[3,2-f][1,4]-oxazepin-5-(4H)-one hydrochloride (10 g, 136 mole) was dissolved in dimethylformamide (150 ml) and heated to reflux. Sulphuryl chloride (20 g, 0.148 mole) was then added dropwise over a period of 40-50 minutes. The reaction was allowed to stir at reflux for 30 minutes following the addition of SO2C12. After cooling, the contents of the flask were partitioned between water (150 ml) and benzene (150 ml). The benzene layer was saved and the water layer extracted with an additional amount of benzene (2 X 50 ml). The benzene extracts were combined and washed with dilute aqueous potassium hydroxide (2 X 50 ml) followed by dilute aqueous hydrochloric acid (2 X 50 ml). The benzene layer was dried over sodium -sulphate concentrated by rotary 'evaporation (-70 C., water aspirator) yielding 2.61 g of crude material. The crude material was recrystallized from isopropyl ether giving 1.25 g (12.6%) of off-white crystals, m.p. 78-790C. Analysis: Calculated or C11H12N2O2Cl2: C,48.02; H,4.40; N, 10.18 Found : C,48.07; H,4.53; N, 10.10 Intermediate 34 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)thione. 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)-one, 6.0 g (0.022 mole) was suspended in 200 ml of toluene. To this suspension was added 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane 2,4-dilsulphide The mixture was heated to reflux with vigorous stirring for 2 hours. Because the reaction was not complete, an additional amount (3.0 g) of 2,4-bis(4-methoxy- phenyl) -1, 3-dithia-2, 4-diphosp'hetane-2 , 4-disulphide was added and the mixture stirred at reflux for 2 hr and left standing for 56 hr at room temperature. The toluene layer was decanted and washed with 50 ml of dilute aqueous sodium. hydroxide and 50 ml of dilute hydrochloric acid. Toluene was removed by rotary evaporation (-80 C., water aspirator). The crude oil was recrystallized from isopropyl alcohol giving 3.5 g (54%) of pale yellow crystals, m.p. 125-1270C. Analysis: Calculated for C11H12N2OSCl2: C,45.37; H,4.15; N,9.62 Found : C,45.40; H,4.20; N,9.71 Intermediate 35 2-(Chloromethyl)-4-cyclohexyl-2,3-dihydropyrido[3,2-f] [1,4]oxazepin-5(4H)-one. A 15 ,g (0.05 mole) sample of sodium 2-[(1-cyclohexyl- 3-azetidinyl)oxy)-3-pyridine carboxylate obtained in Preparation 23 was suspended in 100 ml of chloroform and hydrogen chloride passed in until, a pH of 5.8 remained steady. To the stirred mixture was added 18 g of thionyl chloride. The resulting solution was stirred at room temperature, for 3 hr. An I.R. spectrum showed a.peak at 1770 cm2 which is characteristic of acid chloride. Forty millilitres of triethylamine was added dropwise while cooling to about 25 C. with an ice bath. The chloroform solution was stirred an additional 0.5 hr and was extracted with water, dried over sodium sulphate and concentrated. The residue was chromatographed on a 7. x,20 cm silica column using ethanol as the eluent. The desired material was the first to be removed from the column. The ethanolic solution was, concentrated and the residue crystallized once from ethyl acetate-isopropyl ether and once from isopropyl alcohol. Yield of title compound was 1 g (7%), m.p. 120-122 C. Analysis: Calculated for C15H19N2O2Cl: C,61.12; H,6.50; N,9.50 Found : C,61.11; H,6.62; N,9.32 Intermediate 36 2(2 -chloroethol ) -2, 3-dihydro-4-(phenylmethyl) pyrido [3,2-f][1,4]oxazepin-4(4H)one. The title compound was prepared in crude form in the first part of Example 67. Example 1 2-[2-(Diemthylamino)ethyl]-2,3-dihydro-4-methyl-1,4benzoxazepin-5(4H)one hydrochloride. A solution of 9 g (0.2 mole) of dimethylamine in 250 ml of ethanol was added to 24 g (0.1 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)one in a steel bomb. The mixture was heated at 1000C. for 18 hrs. The solution was concentrated in vacuo and the residue partitioned between ethyl acetate and dilute sodium hydroxide. The ethyl acetate layer was concentrated and the residue comprised substantially of the free base of the title compound was dissolved in methyl isobutyl ketoneisopropanol mixture. The solution was acidified with hydrogen chloride gas to give the title compound, m.p. 188-197 C. Example 2 2-[2-(Dimethylamine)ethyl]-2,3-dihydro-4-methyl-1,4 benzoxazepine-5( 4H)-one. All of the hydrochloride salt obtained in Example was partitioned between chloroform and dilute sodium hydroxide and the chloroform layer concentrated. The residue was crystallized several times from isopropyl ether to give 6 g (21%) of the free base, m.p. 56-760C. Analysis: Calculated for C14H20N2O2: C,67.72; H,8.12; N,11.28 Found : C,67.35; H,8.16; N,11.09 Fxam'ple 3 2,3-Dihydro-4-methyl-2-[2-(4-morpholino)ethyl]-1,4 benzoxazepin-5(4H)-one fumarate [1:1]. To 50 ml of morpholine was added 20 g (0.084 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine 5(lIH)-one. The, solution was refluxed for 5 hrs and then concentrated in vacuo. The residue was dissolved in chloroform, and the solution was washed with dilute sodium hydroxide, dried ovex sodium sulphate and concentrated in vacuo. The residue comprised substantially of the free base of the title compound was reacted with 10.5 g (0.09 mole) of fumaric acid in isopropanol-water. The resulting solid was recrystallized from isopropanol-water to give 21.5 g (64%), m.p. 199-201 C. Analysis: Calculated for C20H28N2O7: C,59.10; H,6.45; N,6.89 Found : C,58.95; H,6.52; N,6.88 Example 4 4-Benzyl-2,3-dihydro-2-[2-(4-morpholino)ethyl]-1,4 benzoxazepin-5( 4H) -one. To 200 ml of morpholine was added 30 g (0.095 mole) of 4-benzyl-2 -( 2 -chloroethyl) 4 ,3-dihydro-1 , 4-benzoxazepin5-(4H)-one. The solution was refluxed for 3 hrs and then concentrated in vacuo. The residue was partitioned between dilute sodium hydroxide and chloroform. The chloroform layer was dried over sodium sulphate and concentrated, in -- vacuo. The solid obtained was recrys'tallized from isopropyl ether-ethyl acetate three times to give 15.2 g of solid (43%), m.p. 97-99 C. Analysis: Calculated for C22H2@N2O3: C,72.10; H,7.15; N,7.64 Found : C,72.25; H,7.22; N,7.64 Example 5 4-Benzyl-2,3-dihydro-2-[2-(methylamino)-3-ethyl]1, 4--benzoxazepin-5 ( 4H))-one fumarate [1:1]. A solution of 5.95 g (0.19 mole) of monomethylamine in 200 ml of ethanol was added to 30 g (O.,095 mole) of 4-benzyl-2-(2-chloroethyl)-2,3-dihydro-1,4-benzoxazepin5(4H)-ohe in a steel bomb. The mixture was heated at 100 C. for 16 hr. The solution was concentrated in vacuo and the residue partitioned between chloroform and dilute sodium hydroxide. The chloroform layer was concentrated and the residue comprised substantially of the free base of the title compound was dissolved in isopropanol and reacted with fumaric acid to give the fumarate. The salt was dried under vacuum at 1000C. until entrapped isopropyl alcohol was removed, m.p. 178-810c. Analysis: Calculated for C23C26N2O@: C.64.77; H,6.15; N,6.57 Found : C,64.87; H,6.20; N,6.62 Example 6 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methyl-1,4benzoxazepine-5(4H)thione hydrochloride [1:1]. To a solution of 7.2 g (0.16 mole) of dimethylamine in 350 ml of absolute ethanol was added 20.4 g (0.08 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine5(4H)thione. The solution was heated in a steel bomb for 18 hr at 100 C. and then concentrated. The residue was partitioned between chloroform and dilute sodium hydroxide. The chloroform layer was dried over sodium:sulphate and concentrated. The solid comprised substantially of the free base of the title compound was reacted with hydrogen chloride gas in ethanol to give the hydrochloride salt. @ The salt was recrystallized from ethanol and dimethyl- formamide followed by three recrystallizations from ethanol to give 7.5 g (280, m.p. 233-236 C. Analysis: Calculated for C14H21N2SOCl: C,55.90; H,7.04; N,9.32 Found : C,55.72; H,7.26; N,8.94 Example 7 4-Benzyl -2-[2-(dimethylamino)ethyl]-2,3-dihydro1,4-benzoxazepin-5(4H)-one monohydrate. -Following the procedure of Example 1, 4-benzyl-2- (2-chloroethyl)-2,3-dihydro-1,4-benzoxazepin-5(4H)-one and dimethylamine were reacted and the free base of.the title compound was obtained in the concentrated residue. Recrystallization from ethanol-water gave the product, m.p. 75-770C. Analysis: Calculated for C20H26N2O5; C,70.13; H,7.65; N,8.21 Found : C,70.02; H,7.53; N,8.25 Example 8 2,3-Dihydro-4-methyl-2-[2-(4-morpholino)ethyl]-1,4 benzoxazepine-5(4H)-thione hydrochloride [1:1]. A solution of 20.4 g (0.08 mole) of 2,3-dihydro-4- methyl-2-(2-chloroethyl)-1,4-benzoxazepin-5(4H)-thione in 60 ml of morpholine was refluxed for 5 hr. then concentrated. The residue was partitioned between dilute sodium hydroxide and chloroform. The chloroform layer was dried over sodium sulphate and coricentrated to give a residue comprised substantially of the free base of the title compound. The hydrochloride salt was prepared in methyl isobutyl ketone-dimet,hylformamide solution with hydrogen chloride gas. The salt was recrystallized from ethanol-dimethylformamide- to give 14 g solid (51%), m.p. 253-2560C. Analysis: Calculated for C15H25N2SO2Cl: C,56.04; H,6.76; N,8.17 Found : C,55.73; H,6.63; N,7.97 Example Q 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylnaphth [2,3-f][1,4]-oxazepin-5(4H)-one oxalate [1:1]. A steel bomb was charged with 5.0 g (0.017 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylnaphth[2,3-f][1,4] oxazepin-5(4E)-one, 50. ml of absolute ethanol and 3.78 g (0.034 mole) of dimethylamine as 40% aqueous solution. The bomb was heated at 100 C. for 16 hr. Volatiles were removed under reduced pressure and the residue partitioned between chloroform and 15% aqueous sodium hydroxide. The chloroform layer was washed twice with water, dried over magnesium sulphate and concentrated'under reduced pressure to give 2.7 g (54%) of viscous yellow oil comprised substantially of the free base of the title compound. The oil was dissolved in isopropyl alcohol and reacted with oxalic acid. The oxalate salt was recystallized from ethanol-water, m.p. 192 -1940C. Analysis: Calculated for C20H24N2O5: C,61.84; H,6.23; N,7.21 Found : C,61.a1; E,6.27; N,7.09 Example 10 2 -r2 -(Dimethylamino) ethyl]-2, 3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepin-5(4H)-one fumarate [2:3]. To 90 g (0.8 mole). of 40% aqueous dimethylamine in a steel bomb was added 25 g (0.09 mole) of 2-(2-chloroethyl)-2,3- dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride. The mixture was heated to 1000C. for 15 hr under mild agitation. The mixture was partitioned using dilute sodium hydroxide and two chloroform extractions. The chloroform layers were combined and concentrated. The residue comprised substantially of the free base of the title compound was dissolved in 200 ml of isopropyl alcohol and 9 g of oxalic acid added. 'The oxalate salt was recrystallized from 95% ethanol to give 18 g. The oxalate salt was then converted to the free base by partitioning between chloroform and dilute sodium hydroxide and evaporating the chloroform layer. The residue, the frei base of the title compound, was dissplved in isopropyl- alcohol and reacted with fumaric acid to give 13 g of white solid (34%), m.p. 146-148 C. Analysis: Calculated for C18H25N5O8: C,53.90; H,5.90; N,9.92 Found : C,53.76; E,6.o2; N,9.96 Example 11 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido r3,2-flC1,41-oxnzepine-5(4B)-thione fumarate rl 11, ethanol [2:1]. To a solution of 32.8 g (0.29 mole) of- 40k aqueous dimethylamine and 100 ml of ethanol in steel bomb was added 15 g (0.058 mole) of 2-(2-chloroethyl)-2,3-dihydro-4- methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-thione. The mixture was heated to 100 C. for 18 hr under mild agitation. The solution was cooled and partitioned between chlofonn and dilute sodium hydroxide. The chloroform layer was dried over sodium sulphate: and concentrated. The residue comprised substantially of the free base of the title compound was dissolved in isopropyl alcohol and reacted with 7 g of fumaric acid. The fumarate salt was recrystallized from isopropyl alcohol to give 19 g (86%), m.p. 105-129 C. A 14 g sample of the salt was recrystallized from ethanol to give 10.5 g yellow'solid, m.p. 103-1180c. The NMR spectra indicates the crystals contain 1/2 mole ethanol., Analysis: Calculated for C36H52N6O11S2: C,53.45; H,6.48; N,10.39 Found : C,53.07; H,6.53; N,I0.23 Example 12 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepine-5(4H)-thione fumarate [1:1]. To a solution of 113 ml (1,0 mole) of 40% aqueous dimethylamine and 326 ml of ethanol in a steel bomb was added 48.4 g (0.189 mole) of 2-(2-chloroethyl)-2,3 dihydro-4-methylpyrido[3,2-f][1,4]-oxazepine-5(4H)-thione The mixture was heated at 1000 C. for.14 hr. The ethanol was removed in a rotary evaporator'iàving' some water in the residue. The residue was dissolved in 200 ml of methylene chloride and washed with three 100 ml portions of 20% aqueous potassium carbonate solution. The combined aqueous layers were extracted with three 150 ml portions of methylene chloride, Methylene chloride solutions were combined and treated with charcoal. Charcoal was filtered off and the filtrate was evaporated to give an oil. The oil was dissolved in 215 ml isopropyl alcohol and the solution was heated to a slow boil. A solution of 21.9 g (0.19 mole) of fumaric'acid in 150 ml of boiling methanol was added to the isopropyl alcohol solution. Crystalline solid was obtained weighing 63.4 g (880. The solid was recrystallized from hot 200 proof ethyl alcohol. The crystals were filtered off and triturated in isopropyl ether at room temperature and, again separated by filtering. After drying in a vacuum oven overnight at 85 C., crystals in the amount of 72.45 g (790, m.p. 130-133 C obtained. Analysis: Calculated for C17H25N5O5S: C,53.53; H,6.08; N,11.02 Found : C,53.23; H,6.11; N,10.64 Example 13 4-Benzyl-2,3-dihydro-2-[2-(4-morpholino)ethyl]-1,4 benzoxazepine-5(4H)-thione. To a suspension of a finely ground mixture of 2.9 g (0.013 mole) of phosphorus pentasulphide and 2.9 g of potassium sulphide in 75 ml of dry toluene was added 12 g (0.033 mole) of 4-benzyl-2,3-dihydro-2-[2-(4-morpholino) ethyl]-1,4-benzoxazepine-5(4H)-one. The mixture was stirred at reflux for 10 hr. and filtered. The filtrate was concentrated and the residue crystallized from isopropyl ether-toluene to give 2.54 g (20%), m.p. 2362380c. Analysis: Calculated for C22H26N2O2S: C,69.08; H,6.85; N,7.32 Found : C,69.60; H,6.96; N,7.15 Example 14 2,3-Dihydro-4-methyl-2-[2-(methylamino)ethyl]-1,4benzoxazepin-5(4H)-one fumarate [1:1]. Following the procedure ef Example 5, 50 g (0.21 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin5(4H)-one and 13.0 g (0.42 mole) of monomethylamine (in 400 ml ethanol) were reacted to give the free base of the title compound which was reacted with fumaric acid to give, after isolation and recrystallization from ethyl alcohol, 17 g (23%) of the title compound, m.p. 154-156 C. Analysis: Calculated for C17H22N2O6: C,58.27; H,6.33; N,8.00 Found : C,58.34; H,6.52 N,7.82 Example 15 2,3-Dihydro-4-methyl-2-[2-(methylamino)ethyl]-1,4benzoxazepin-5(4H)-one. 2,3-Dihydro-4-methyl-2-[2-(methylamino)ethyl]-1,4 benzoxazepin-5(4fl)-one fumarate was converted back to the free base by partitioning in dilute sodium hydroxide and chloroform. Evaporation of the chloroform layer and distilling, b.p. 182 /0.2 mm, gave 4.3 g of the product. Analysis: Calculated for C13H18N2O2: C,66.64; H,7.74; N,11.96 Found : C,66.48; H,7.69; N,11.88 Example 16 2,3-Dihydro-2-[2-(4-hydroxy-4-phenyl)-piperidinylethyl]-4-methyl-1,4-benzoxazepine-5(4H)-thione (and hydrochloride salt.) A suspension of 10.7 g (0.078 mole) of potassium carbonate, 15.7 g (0.078 mole) of 4-hydroxy-4-phenyl- piperidine and 19.8 g (0.078 mole) of 2-(2-chloroethyl)- 2,3-dihydro-4-methyl-1,4-benzoxazepine-5(4H)-thione in 200 ml of n-butanol was refluxed dvernight. The mixture was filtered and the filtrate concentrated in vacuo. The residue was dissolved in ethanol-ligroin and reacted with hydrogen chloride gas to give the hydrochloride salt which was recrystallized from ethanol-dimethyl foramide. he hydrochloride salt was converted back to the free base by partitioning in chloroform and dilute sodium hydroxide and evaporating the chloroform. Recrystal- lization twice from isopropyl alcohol gave 9.27 g (30%) product free base, m.p. 142-148 C Analysis: Calculated for C23H26N2O2S: C,69.66; H,7.12; N,7.07 Found : C,69.78; H,7.18; N,7.00 Example 17 2,3-Dihydro-4-methyl-2-[2-[1-(4-phenyl-1,2,3,6tetrahydro)pyridinyl]ethyl]-1,4-benzoxazepine-5(4H)thione. A suspension of 24.3 g (0.176 mole) of potassium carbonate, 11.5 g (0.059 mole) of I{-phenyl-3,4-tetrahydro pyridine and 15 g (0.059 mole) of 2-(2-chloroethyl)-2,3- - dihydro-4-methyl-1,4-benzoxazepine-5(4H)-thione and enoug n-butanol to form a slurry were refluxed for 72 hr. The reaction mixture was filtered hot and the filtrate cooled to room temperature and refiltered. The last filtrate was concentrated and the residue dissolved in ethyl acetate. The crystals obtained on cooling were recrystallized from ethyl acetate to give 7 g of product (31%), m.p. 153-155 C. Analysis : Calculated for C23H26N2OS: C,72.98; H,6.92; N,7.40 Found : C,73.36; H,7.01; N,7.47 Example 18 8-Chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benzoxazepine-5(4H)-thione hydrochloride [1:1]. A solution of. 9.8 g (0.04 mole) of 8-chloro-2 (2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine-5 (4H)-thione in 50 ml of absolute ethanol and 10 ml of a 40% agueous solution of dimethylamine were mixed and heated in a steel bomb at 100 C. for 16 hr. The ethanol was evaporated under reduced pressure and the residue dissolved in chloroform-and partitioned with 10% sodium hydroxide solution. The chloroform layer was evaporated under reduced pressure to give an amorphous solid. The solid was dissolved in 6N hydrochloric acid and the solution washed with ethyl acetate. The aqueous layer was basified with 50% sodium hydroxide and extracted with ethyi acetate. The ethyl acetate layer was evaporated under reduced pressure to give a, viscous oil comprised substantially of the free base of the title compound which was dissolved in absolute ethanol and reacted with ethereal hydrogen chloride, The hydrochloride=salt was recrystalwzed from ethanol to give 30 g (25%) product, m.p. 196-199 C. Analysis: Calculated for C14H20N2Cl2OS: C,50.15; H,6.01; H,8.35 Found : C,50.15; H,6.18; N,8.07 Example 19 8-Chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benxazepin-5(4H)-one oxalate [1:1]. A solution of 10 g (0.037 mole) of 8-chloro-2-(2chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)one in 50 ml of absolute ethanol and 10 ml of 10,% aqueous solution of dimethylamine were mixed and heated in a steel bomb at lOO0C. for 16 hr. The solution was concentrated under reduced pressure and the residue dissolved in chloroform and partitioned with 15k sodium hydroxide (2 washes). The chloroform layer was dried over magnesium sulphate and evaporated under reduced pressure to give an oil, comprised substantially of the free base of the title compound. The oil was dissolved in absolute ethanol and reacted with oxalic acid. The oxalate salt was recrystallized from ethanol in the amount of 4 g (38%),, m.p. 198-210 C. Analysis: Calculated for C1621N2ClO8: C,51.55; H,5.68; N,7.51 Found : C,51.07; H,5.69; N,7.43 Example 20 7-Bromo-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benzoxazepine-5(4H)-one oxalate [1:1]. To a solution of 3.0 g (0.01 mole)of 7-bromo-2- ( -chloroethyl) -2 , 3-dihydro-4 -methyl-1, 4 -benzoxazepin5(4H)-one in 50 ml of absolute ethanol was added 2:2 ml of a 40% aqueous solution of dimethylamine, The reaction mixture was heated in a stainless steel bomb at 100 C. for 16 hr and concentrated under reduced pressure. The residue was partitioned between chloroform and 15% sodium hydroxide solution. The chloroform layer was separated and extracted with 3N aqueous hydrochloric acid. The acid layer was basified with 50k aqueous sodium hydroxide and extracted with chloroform. The chloroform was evaporated under reduced pressure to give 2.4 g (73%) viscous brown oil, the free base of the title compound. The oil was dissolved in isopropyl alcohol and reacted with oxalic acid. The oxalate salt was.recrystallized from isopropyl alcohol/ water to give the title salt, m.p. 192-1940C. Analysis: Calculated for C16H21O6BrN2: C,46.06; H,5.07; N,6.71 Found : C,46.00; H,5.10; N,6.68 Example 21 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylnaphth [2,1-f][1,4]oxazepin-5(4H)-one oxalate [1:1]. A solution of 8 g (0.028 ,mole) of 2-(2-chloroethyl) 2,3-dihydro-4-methylnaphth[2,1-f][1,4]oxazepin-5(4H)-one and 6.2 g of 40% dimethylamine (0.055 mole) in 100 ml of ethanol was heated in a steel bomb to 1000c. for 18 hr. The resulting solution was partitioned between methylene chloride and dilute sodium hydroxide solution. The methylene chloride layer was dried over sodium sulphate and concentrated. The residue comprised substantially of the free base of the title compound was dissolved in isopropyl alcohol and reacted with 2.6 g oxalic acid. The oxalate salt obtaine'd was ,r,ecrystallized from isopropyl alcohol in water, m.p. 206-209 C. Analysis : Calculated for C20H24N2O0: C,61.85 ; H,6.23 ; N,7.21 Found : C,61.61 ; H,6.26 ; N7El3 Example 22 When in the procedure of Example 10 equal molar amounts of the following are substituted for 2-(2-chloroethyl)- 2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride: 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[4,3-f] [1,4]-oxazepin-5(4H)-one hydrochloride, 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,4-f] [1,4]-oxazepin-5(4H0-one hydrochloride, and 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[2,3-f] [1,4]-oxazepin-5(4H)-one hydrochloride, there are obtained: : 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [4,3-f][1,4]-oxazepin-5(4H)-one fumarate, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,4-f][1,4]-oxazepin-5(4H)-one fumarate, and 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [2,3-f][1,4]-oxazepin-5(4H)-one fumarate. Example 23 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [4,3-f] [1,4]-oxazepine-5(4H)-thione hydrochloride [2:3]. To a solution of 0.5 g (0.002 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[4,3-f][1,4]-oxazepine5(4h)-thione in 20 ml of ethyl alcohol was added 2 ml of 40% aqueous dimethylamine. The mixture was heated in a steel bomb to 100 C. for 14 hr. The resulting solution was filtered and concentrated. The residue was dissolved in isopropyl alcohol and a few drops of ethereal hydrogen chloride, were added. The hydrochloride salt crystals were recrystallized by dissolving in ethyl alcohol and boiling while replacing the ethyl alcohol with isopropyl alcohol. The yield of product was 0.3 g (47%), m.p. : decomp. above 200 C. Analysis : Calculated for C26H41N@O2S2Cl5 : C, 48.78 ; H, 6.46 ; N, 13.13 : C,49.34 : H, 6.47 ; Found N, 13.03 Example 24 2-[2-(Diethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepine-5(4H)-thione. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,41-oxazepine-5(4H)-thione and diethylamine in ethanol are heated together to obtain the title compound. Example 25 2-r2-(Dmethyl aminoéthyllW ,7-dihydro-4-methylnaghth [2,3-f][1,4]-oxazepine-5(4H)thione oxalate [1:1] hemihydrate. To a solution of 15 g (0.05 mole) of 2-(2-chloroethyl) 2,3-dihydro-4-methylnaphth[2,3-f][1,4]-oxazepine-5(4H) thione in 50 ml of absolute ethanol was added 10 ml of a 45% aqueous solution of dimethylamine. The solution was heated in a steel bomb for 16 hr. The ethanol was evaporated under reduced pressure and the residue partitioned between chloroform and 15k aqueous sodium hydroxide. The chloroform layer. 'was separated and extracted with 3N aqueous hydrochloric acid. The acid layer was basified with 50% aqueous sodium hydroxide and extracted with chloroform. The chloroform solution was concentrated under reduced pressure and -the 'residue was dissolved in isopropyl alcohol and reacted with oxalic acid. The salt was recrystallized from isopropyl alcohol and water to give the title compound, m.2 115-1180C. Analysis : Calculated for C40H50N4O11S2 : C, 58.09 ; H, 6.09 ; N, 6.77 Found : C, 58.42 ; H, 5.85 ; N,6.70 Example 26 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-7,9-diiodo-4 methyl-l, 4-benzoxazepin-5 ( H) -one. Utilizing the procedures of Example 1 and 2 and substituting 2-(2-chloroethyl)-7,9-diiodo-4-methyl-2,3dihydro-4-methyl-1,4-benzoxazepin-5(4H)-one for 2-(chloro ethyl)-4-methyl-2,3-dihydro-1,4-benzoxazepin-5(4H)-one, the title compound is obtained, Example 27 7-Chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benzoxazepin-5(4H)-one oxalate [1:1]. To a solution of 9.0 g (0.053 mole) of 7'-chloro-2- (2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)one in 50 ml absolute ethanol was added 7 g (0.066 mole) of a 45% aqueous solution of dimethylamine. The solution was heated in a stainless steel bomb at 100 C. for 14 hr. The reaction mixture was conceritated under reduce pressure and the residue was pa,rtitioned between chloroform and 15 aqueous sodium hydroxide. The chloroform layer was separated and evaporated under reduced pressure to give a viscous brown oil. The oil was dissolved in isopropyl alcohol and oxalic acid added. Recrystallization from isopropyl alcohol/water gave 7.0 g (57%) oxalate salt, m.p. 199-200 C. Analysis ; Calculated for C18H21N2O@Cl : C,51.55 ; , 5.68@ N, 7.51 Found : C,51.52 ; H,5.72, N.7.44 Example 28 2-(Dimethylamino)methyl-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepin-5(4H)-one. When in the procedure of Example 10, 2-chloromethyl2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one is substituted for 2-(2-chloroethyl)-2,3-dihydro-4-methyl- pyrido[3,2-f][1,4]-oxazepin-5(4H)-one, the title compound is prepared and is isolated if desired as a pharmaceutically acceptable salt. Example 29 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepine-5(4H)-thione methiodide. 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepine-5(4H)-thione fumarate [1:1], ethanol [2:1], 3.8 g (0.01 mole) was partitioned ,between chloroform and dilute sodium hydroxide. The chloroform extract was dried over sodium sulphate and concentrated. The residue was dissolved in 15 ml of methyl isobutyl ketone and added to a solution of 1.4 g (0.01 mole) of methyl iodide in 15 ml of isobutyl ketone. Recrystallization from o% methanol - 50% methyl isobutyl ketone gave 2.5 g (78%) of the product, m.p. 221-2250C. Analysis : Calculated for C14H22N3OSI : C, 41.28 ; H, 5.44 ; N, 10.31 Found : C, 41.29 ; H, 5.51 ; N, 10.30 Example 30 7-Chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benzoxazepine-5(4H)-thione oxalate [1:1] hemihydrate. To a solution of 8.0 g (0.027 mole) of 7-chloro-2- (2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine-5(4H)thione in 50 ml of absolute ethanol was added 6 ml (0.054 mole) of 40% agueous solution of dimethylamine. The solution was, heated in a steel bomb at 90 C. for 14 hr. The ethanol was removed under reduced pressure and the residue was partitioned between chloroform and aqueous sodium hydroxide. The chloroform layer was concentrated to give a viscous yellow oil. The oil was dissolved in isopropyl alcohol and reacted with oxalic acid. .The oxalate salt immediately precipitated. The mixture was heated and a small amount of water was added to dissolve the salt. A white crystalline powder was obtained, m.p. 150-151 C. Analysis : Calcualted for C32H44N4Cl2O11S2 : C, 48.30 ; H, 5,57 ; N, 7.04 Found : C, 48.74 ; H, 5.34 ; - N,6.95 Example 31 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylnaphth [2,1-f][1,4]-oxazepine-5(4H)-thione hydrochloride [1:1]. To a solution of 15.0 g (0.05 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylnaphth[2,1-f][1,4]-oxazepine 5(4H)-thione in 50 ml of absolute ethanol was added 10 g of a 40% aqueous solution of dimethylamine. The resulting solution was heated in a steel bomb at 100 C. for 40 hr and concentrated under reduced pressure. The residue was partitioned between 15% aqueous sodium hydroxide and chloroform. The chloroform layer was evaporated and the residue partitioned between 3N hydrochloric acid and chloroform. The aqueous layer was made alkaline with 50% sodium hydroxide and extracted with chloroform. The chloroform extract was concentrated and the residue dissolved in isopropyl alcohol. Ethereal hydrogen chloride was added. Recrystallization of the-precipitate from isopropyl alcohol/water gave 3.0 g (20%) of' the product, m.p. 238-240 C. Analysis : Calculated for C18H23N2CloS: C, 61.61 ; H, 6.61 ; N, 7.98 Found : C, 61.80 ; H, 6.61 ; N, 7.91 Example 32 When in the procedure of Example 11 equal molar amounts of the following are substituted for 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepine5(4H)-thione : 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,4-f] [1,4]=oxazepine-5(4H)-thione, and 2-(2-chloroethyl-2,3-dihydro-4-methylpyrido[2,3-f] [1,4]-oxazepine-5(4H)-thione, there are obtained: a) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,4-f][1,4]-oxazepine-5(4H)-thione fumarate, and b) 2-12-(dimethylamino)ethylI-2,3-dihydro--methylpyrido [2,3-f][1,4]-oxazepine-5(4H)-thione fumarate. Example 35 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-7-methoxy-4methyl-1,4-benzoxazepin-5(4H)-one oxalate [1:1] hemihydrate. To a solution of 3.0 g (0.011 mole) of 2-(2-chloroethyl)-2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin5(4H)-one in 50 ml of absolute ethanol was added 3.0 g of a 40% aqueous solution of dimethylamine. The reaction mixture was heated in a stainless steel bomb at 100 C. for 16 hr, cooled and evaporated under reduced pressure. The residue was partitioned between chloroform and 15% sodium hydroxide solution. The chloroform layer was concentrated and the residue, the free base, was dissolved in isopropyl alcohol and reacted With oxalic acid. The resulting oxalate salt was recrystallized from isopropyl alcohol/H2O to give 1.9 g (45%) of the title salt, m.p. 176-1780c. Analysis : Calculated for C34H50N4O15 : C,54.10 ; H, 6.67, Found :C,54.29; H, 6.59; N,7.53 Example 34 7-Bromo-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benzoxazepine-5(4H)-thione oxalate [1:1] monohydrate. To a solution of 13 g (û.04 mole) of 7-bromo-2-(2 chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine-5(4H)thione in 50 ml of absolute ethanol was added 8 ml of a 45% agueous solution of dimethylamine. The solution was heated at - 1000C. in a steel bomb for 16 hr. The ethanol was evaporated under reduced pressure and the residue partitioned between ethyl aceta'te and 3N aqueous hydrochloric acid. The aqueous extract was basified with o% aqueous sodium hydroxide and extracted with chloroform. The chloroform was 'concentrated under reduced pressure. The residue, the free base of the title compound, was dissolved in isopropyl alcohol and reacted with oxalic acid. The oxalate salt was recrystallized from 95% ethanol to give the title salt, m,p. 155-157 C. Analysis : Calculated for C32H40N4Br2O12S2 : C, 42.58 ; H, 5.14 ; N, 6.12 Fond : C, 42.93 ; H, 4.79 N, 6.19 Example 35a to h 'When in the procedure of Example 27, equal, molar amounts of the following are subs,tituted for 7-chloro-2 (2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin 5(2iE)-one, 2-(2-chloroethyl)-4-cyclohexyl-2,3-dihydro-1,4 benzoxazepin-5(4H)-one, 2 -(2-chloroethyl) -2, 3-dihydro-4-ethyl-l, &num; ;-benz- oxazepin-5( 4R) -one, S?-(2 -6hloroethyl) -2, 3-dihydro-a-isopropyl-1, 4-benz- oxazepin-5( 4H)-one, 2-(2-chloroethyl)-4-(4-chlorobenzyl)-2,3-dihydro 1,4-benzoxazepin-5(4H)-one, 2-(2-chloroethyl)-2,3-dihydro-4-(4-methylbenzyl) 1,4-benzoxazepin-5(4H)-one, 2 -( ) hloroethyl ) -2, 5-dihydro-4-t3, 5-dimethoxybenzylj,- 1, 4-benzoxazepin-5 ( H) -one, 2-(2-chloroethyl)-2,3-dihydro-4-(3-trifluoromethyl benzyl)-1,4-benzoxazepin-5(4H)-one, and 2-(2-chloroethyl)-2,3-dihydro-4-(4-nitrobenzyl) 1,4-benzoxazepin-5(4H)-one, there are obtained: : a) 4-cyclohexyl-2-[2-(dimethylamino)ethyl]-2,3-dihydro 1,4-benzoxazepin-5(4H)-one oxalate, b) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-ethyl-1,4 benzoxazepin-5t 4H) -one oxalate, c) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-isopropyl 1,4-benzoxazepin-5(4H)-one oxalate, d) 4-(4-chlorobenzyl)-2-[2-(dimethylamino)ethyl]-2,3 dihydro-1,4-benzoxazepin-5(4H)-one oxalate, e) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(4-methyl benzyl)-1,4-benzoxazepin-5(4H)-one oxalate, f) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(3,5 dimethoxybenzyl)-1,4-benzoxazepin-5(4H)-one oxalate, g) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-[(3 (trifluoromethyl)benzyl]-1,4-benzoxazepin-5(4H) one oxalate, and h) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(4-nitro benzyl)-1,4-benzoxazepin-5(4H)-one oxalate. Example 36a toh When in the procedure of Example 10, equal molar amounts of the following are substituted for 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-oxazepin 5 ( 4E) -one hydrochloride, 2 -(2 -chloroethyl) cycl ohexyl-2, 3-dihydropyrido [3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, 2-(2 -chloroethyl) -2 ,3-dihydro-4-ethylpyrido [3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, 2-(2-chloroethyl)-2,3-dihydro-4-isopropylpyrido [3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, 2(2 -chloroethyl) )-4 -( 4 -chlorobenzoyl ) -2 , 3-dihydro Pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, 2-(2-chloroethyl)-2,3-dihydro-4-(4-methylbenzyl) pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, 2-(2-chloroethyl)-2,3-dihydro-4(4-methoxybenzyl) pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, 2-(2-chloroethyl)-2,3-dihydro-4-(3-trifluoromethyl benzyl)pyrido[3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, and 2 -(2 -chloroethyl) -2, 3-dihydro-4-( 4-nitrobenzyl) -pyrido [3,2-f][1,4]-oxazepin-5(4H)-one hydrochloride, there are obtained: : a) 4-cyclohexyl-2-[2-(dimethylamino)ethyl]-2,3-dihydro pyrido[3,2-f][1,4]-oxazepin-5(4H)-one fumarate, b) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-ethyl pyrido[3,2-f][1,4]-oxazepin-5(4H)-one fumarate, c) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-isopropyl pyrido[3,2-f][1,4]-oxazepin-5(4H)-one fumarate, d) 4-(4-chlorobenzyl)-2-[2-(dimethylamino)ethyl] 2,3-dihydro-pyrido[3,2-f][1,4]-oxazepin-5(4H) one fumarate, e) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(4-methyl benzyl)-pyrido[3,2-f][1,4]-oxazepin-5(4H)-one fumarate, f) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(4 methoxybenzyl)-pyrido[3,2-f][1,4]-oxazepin-5 (4H)-one fumarate, g) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(3-tri fluoromethylbenzyl)-pyrido[3,2-f][1,4]-oxazepin 5(4H)-one fumarate, and h) 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-(4-nitro benzyl)-pyrido[3,2-f][1,4]-oxazepin-5(4H)-one fumarate. Example 37a to d @ When in the procedure of Example 3, equal molar. amounts of the following are substituted for morpholine: pyrrolidine, piper'idine, piperazine, and 4-methyl-piperazine, there are obtained: a) 2 , 3-dihydro-4-methyl-2 -r2 -( l-pyrrolidino)ethyl3 1,4-benzoxazepin-5(4H)-one fumarate, b) 2,3-dihydro-4-methyl-2-[2-(1-piperidino)ethyl] 1,4-benzoxazepin@-5(4H)-one fumarate, c) 2,3-dihydro-4-methyl-2-[2-(1-piperazino)ethyl] - 4-benzoxazepin -4(4H)-one fumarate, and d) 2,3-dihydro-4-methyl-2-[2-(4-methylpiperazin-1-yl) ethyl]-1,4-benzoxazepin-5(4H)-one fumarate. Example 38 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-thiazepin-5(4H)-one dihydrochloride. A solution of 1.5 g (0.0058 'mole) of 2-(2-chloroethyl)2,3-dihydro-4-methylpyrido[3,2-f][1,4]-thiazepin-5(4H)-one in 20 ml of dimethylamine was stirred at 25@C. in a sealed container for 72 hr. The excess dimethylamine was allowed to evaporate and the residue was partitioned between chloroform and dilute sodium hydroxide. The chloroform layer was concentrated and the residue, the free base of the title compound, was dissolved in isopropyl alcohol and reacted with hydrogen chloride. The resulting hydrochloride salt weighed 1.5 g (77s, m.p. > 2500C. Analysis : Calculated for C18H21N#OSCl2 : C, 46.16 ; H, 6.27 N, 12.42 Found : C, 45.68 ; H, 6.18 ; N. 12.35 Example 39 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-thiazepine-5(4H)-thione oxalate. A solution of 1.5 g (0.005 mole) of 2-(2-chloroethyl)- 2,3-dihydro-4-methylpyrido[3,2-f][1,4]-thiazepine-5(4H)thione in 40 ml of dimethylamine was stirred at 25 C. in a sealed container for 96 hr. The dimethylamine was allowed to evaporate and the residue was parti,tioned between methylene chloride and dilute sodium hydroxide. The chloroform layer was concentrated and the residue, the free base of the title compound, was reacted with 0.4 g oxalic acid in a solution of 30 ml of 90-100 isopropyl alcohol water. The resulting crystals were recrystallized from the same solvent to give 1 g of the product, m.p. 191-1930C. Analysis : Calculated for C15H21N@S2O4 : C, 48.50 ; H, 5.70 ; N, 11.33 Found : C, 48.49 ; H, 5.84 ; N,l0.99 Example 40 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,4-f][1,4]oxazepin-5(4H)-one oxalate (1:2) hemihydrate. .A solution of 5 g (0.02 mole) of 2-(2-chloroethyl) 2,3-dihydro-4-methylpyrido[3,4-f][1,4]oxazepin-5(4H)-one, in 25 ml of dimethylamine was placed in a sealed vessel and stirred for 72 hr. The vessel was opened and the excess dimethylamine allowed to evaporate. The residue was dissolved in chloroform and the solvent was stripped off in vacuo to remove excess dimethylamine. The residue was partitioned between dilute sodium hydroxide and ethyl acetate. The ethyl acetate solution was concentrated and the residue was treated with 3 g (0.033 mole) of oxalic acid in 50 ml of isopropyl alcohol and enough water to dissolve the salt while boiling. The resulting crystals were recrystallized from the same solvent. Yield of product was 5.3 g (60%), m.p. 179-181 C. Analysis : Calculated for C34H48N6O21 : C, 46.48 ; H, 5.52 ; N,9.58 Found : C, 46.58 ; H, 5.70 N,9.61- Example Ill 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,4-f][1,4]oxazepine-5(4H)-thione oxalate (1:2). A 4 g (0.009 mole) sample of 2 -C2 (dimethylamino) ethyl3- 2,3-dihydro-4-methylpyrido[3,4-f][1,4]oxazepin-5(4H)-one oxalate (1:2) hemihydrate was partitioned between dilute sodium hydroxide and chloroform. The aqueous. layer was extracted three times and the combined chloroform extracts . were dried over sodium sulphate and concentrated. The residue was dissolved in 200 ml of dry toluene and again concentrated in vacuo to effect drying. The residue was dissolved in dry pyridine (.10 ml) and treated with 2.8 g (0.01 mole) of phosporus pentasulphide. The mixture was stirred at reflux for 20 hr. .The cooled mixture was partitioned between dilute sodium hydroxide and chloroform. The aqueous layer was extracted three times with chloroform. The combined chloroform extracts were dried over sodium sulphate and concentrated. One gram of the residue was treated with 0.6 g of oxalic acid in isopropyl alcohol water. The resulting crystals were collected by filtration'. Yield of oxalate salt was 0.37' g., m.p. 111-114 C. Analysis : Calculated for C17H23N3SO9 : C, 45.84 ; H, 5.20 ; N, 9.43 Found : C, 45.46 ; H, 5.38 N,9.28 Example 42 : 2-(2-Aminopropyl)-2,3-dihydro-4-methyl-pyrido[3,2-f] [1,4]-oxazepin-5(4H)-one, oxalate [1:1]. 2,3-Dihydro-4-methyl-5(4H)-oxopyrido[3,2-f][1,4] oxazepine-2-propanenitrile, 5 g (0.22 mole, in 150 ml of ethanol was treated with about 1.5 g of wet Raney nickel. The mixture was hydrogenated in a Parr apparatus at 60 C. and 40 psi. The mixture was cooled and filtered and the filtrate concentrated. The residue was treated with 3.9 g of oxalic acid in 130 ml of boiling isopropyl alcohol containing 2 ml of water. The hot solution was filtered @@ and allowed to cool. The resulting solid was recrystal- lized from ethanol. Yield of oxalate bemihydrate was 3 g (43%), m.p. 126-134 C. Analysis : Calculated for C28H40N6O7 : ,50.30 ; H, 6.03 N, 12.57 Found : C, 50.46 ; H, 5.71 ; N, 12.21 Example 43 2,3-Dihydro-4-methyl-2-[2-(4-morpholinyl)ethyl]pyrido[3,2-f][1,4]oxazepin-5(4H)-one maleate [1:1]. 2-(2 Chloroethyl) -2 ,3-dihydro-4-methylpyrido±3 2 2-f) [1,4]oxazepin-5(4H)-one hydrochloride, 16 g (058 mole) was dissolved in morpholine (30 ml) and stirred overnight at room temperature. To the solution was added dilute sodium hydroxide solution (50 ml) and the resulting mixture extracted with chloroform (3 X 30 ml). The chloroform was removed on the rotary evaporator with aspiration. The residual morpholine was removed in vacuo at 50 C. (rotary evaporator). To the residual free base (15.5 g, .053 mole) was added isopropyl alcohol (1 liter) and maleic acid (9.24 g g, .080 mole). The mixture was heated to boiling and the clear solution cooled at 20 C. for several hours. The resulting crystals, 16 g (68.1%), were recrystallized from isopropyl alcohol, m.p. 163-1650C. Analysis: Calculated for C19H25N3O7 : C,56.0l; H,6.18; N, 10.31 Found : C, 55.71 ; H, 6.21 ; N, 10.18 Example 44 2,3-Dihydro-4-methyl-2-[2-(1-pyrrolidinyl)ethyl]pyrido [3,2-f][1,4]-oxazepin-5(4H)-one fumarate [1:1]. A sample of 2-(2-chloroethyl)-2,3-dihydro-4-methyl- pyrido[3,2-f][1,4]-oxazepine-5(4H)-one hydrochloride, 16 g (o.058 mole), was dissolved in 65 ml of pyrrolidine. The stirred solution was heated to 800C. for 3 hr. The solution was cooled to room temperature and dilute sodium hydroxide: solution (50 ml) was added. The resulting solution was extracted with chloroform (3 X 30 ml) and concentrated in vacuo. The residue was taken up in boiling isopropyl alcohol (500 ml/ and fumaric acid (9.2 g, .079 mole) was added. ,The solution was filtered hot and the filtrate cooled to 20 C. for several hours. The resulting crystals, 14 g (47.8%) were collected and recrystallized from isopropyl alcohol, m.p. 147-149 C. Analysis : Calculated for C23O10N3H29 : C, 54.43 ; H, 5.76 ; N,8.28 Found : C,54.38; H,5.83; N,8.27 Example 45 2-[2-(Dibutylamino)ethyl]-2,3-dihydro-4-methyl-pyrido [3,2-f][1,4]oxazepin-5(4H)-one maleate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepine-5(4H)-one hydrochloride, 16 g (0.058 mole) was dissolved in dimethylformamide (30 ml) and di-n-butylamine (30 ml). The solution was stirred at 90 C. for 3 hr at 100 C. for 2.5 hr. The solution was cooled and to it was added 50 ml of dilute sodium hydroxide solution. The resulting mixture was extracted with chloroform (3 X 50 ml). The chloroform was removed on the rotary evaporator with water aspiration at 50 C. Residual dimethylformamide and di-n-butylamine were removed at low vacuum and 50 C. (rotary evaporator0. To the residual free base, 13.8 g (0.041 mole) was added isopropyl alcohol (900 ml) and oxalic acid, 5.6 g (0.062 mole) and the solution heated to boiling. The clear solution was cooled overnight at 200C. and filtered to give 13.6 g (56.5%) of crystals which were recrystallized from isopropyl alcohol, m.p. 195-196 C. Analysis: Calculated for C21H33N3O6 : C,59.59; E,7.85; N, 9.72 Found : C, 59.37 ; H, 7.91 ; N, 9.86 Example 46 2-[2-(Diethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)-one oxalate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepin-5(4H)-one hydrochloride, 16 g ().058 mole). was suspended in diethylamine (30 ml). The suspension was stirred for 72 that room temperature:. The mass spectrum indicated that the reaction had progressed 33% at this point. The mixture was then heated to reflux for 6 hr. Diethylamine was removed by rotary evaporation (70 C. water aspirator). The residue was taken up in chloroform (100 ml) and washed with dilute aqueous sodium hydroxide (2 X 30 ml). The organic layer was concentrated by rotary evaporation (70 C, water aspirator). The residue was dissolved in boiling isopropyl alcohol and treated with oxalic acid. Upon cooling, 18.6 g (87.7%) of light brown crystals were collected (m.p. 150 -155 C.). A sample was recrystallized three more times form isopropyl alcohol, m.p. 156-157 C. Analysis : Calculated for C17H25N3O6 : C, 55.57 ; H, 6.86 ; N, 11.43 Found : C,55.28; E,6.85; N, 11.27 Example 47 2,3-Dihydro-4-methyl-2-[2-(1-piperidinyl)ethyl]pyrido [3,2-f][1,4]oxazepin-5(4H)-one oxalate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepin-5(4H)-one hydrochloride, 4 g (O.015 mole) was dissolved in piperidine (30 ml) and heated to'800C. with stirring for 20. minutes. The'piperidine was removed by rotary evaporation (850C, vacuum pump) and the residue taken up in chloroform (50 ml). The organic layer was washed with dilute aqueous sodium hydroxide (2 x 20 ml) and concentrated by rotary evaporation (800C, water aspirator). The resulting oil was taken up in hot isopropyl alcohol and treated with oxalic acid. Upon cooling, crystals of the oxalate salt were collected and recrystallized from isopropyl alcohol, to give 3.4 g (62%) of pale brown crystals, m.p. 133-136 C. Analysis : Calculated for C18H25N3O6 : C, 56.98 ; H, 6.64 ; N, 11.07 Found : C, 56.95 ; H, 6.87 ; 'N, 10 Example 48 2,3-Dihydro-4-methyl-2-[2-[methyl(phenylmethyl)amino] ethyl]pyrido[3,2-f][1,4]oxazepin-5(4H)-one maleate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepin-5(4H)-one hydrochloride, 4 g (0.015 mole) : was dissolved in methyl benzyl amine (30 ml) and heated to 800C. with stirring. After three hours, the excess amine was removed by rotary evaporation (90 C, vacuum pump). The residual oil was taken up in chloroform (40 ml) and washed with dilute aqueous sodium hydroxide (30 ml). The chloroform layer was concentrated by rotary evaporation (90 C, water aspirator). The residual oil was dissolved in hot isopropyl alcohol and treated with maleic acid. Upon cooling, 4.23 g (66%) of pale brown crystals were collected, m.p. 167-1690c.. Analysis : Calcualted for C25H27N3O6 : C, 62.57 ; H, 6.16 ; N,9.52 Found : C,62.28; H,6.16; N, 9.24 Example 49 2,3-Dihydro-4-methyl-2-[2-(methylphenylamino)ethyl] pyrido[3,2-f][1,4]oxazepin-5(4H)-one. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepin-5(4H)-one hydrochloride, 4.00 g (0.015 mole) was dissolved in N-methylaniline (30 ml) and heated to 95 C. with stirring for 2 days. Excess N-methylaniline was removed by rotary evaporation (95 C, vacuum pump). The residue was taken up in chloroform (80 ml) and washed with dilute aqueous sodium hydroxide (30 ml) The chloroform layer was decolourised with activated carbon and dried over sodium sulphate, filtered and concentrated by rotary evaporation. The remaining residue was dissolved in ethyl acetate (50 ml) and purified by high pressure liguide chromatography using a silica gel column and ethyl acetate as the eluent. After purification, crystals formed from ethyl acetate. These crystals were recrystallized from ethyl acetate, giving 1.40 g (3'.l%) of plae brown' crystals; Analysis : Calculated for C18H21N3O2 : C, 69.43 ; H, 6.79 ; N, 13.49 Found : C, 69.31 ; H, 6.77 ; N, 13.54 Example 50 2-[2-(2,5-Dimethyl-1-pyrrolidinyl)ethyl]-2,3-dihydro4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)-one fumarate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepin-5 (4H)-one, 5.0 g (0.021 mole), was dissolved in 25 ml of ab'solute,ethanol and 3 g (0.03 mole) of 2,,5- dimethylpyrrolidine was added. The solution was heated to 75 C. for 48 hrs with stirring. Because the reaction was incomplete at this time, an additional amount of 2, 5- dimethylpyrrolidine (1.00 g, 0.01 mole) was added and the reaction continued. After 5 days, the reaction was still incomplete and more 2,5-dimethylpyrrolidine (1.00 g, 0.01 mole) was added. The reaction appeared complete 2 days later. Solvent was removed by rotary evaporation (800C., water aspirator); Excess 2,5-dimethylpyrrolidine was removed by rotary evaporation (800C, vacuum pump). The residue was taken up in chloroform (200 ml) and washed with dilute aqueous sodium hydroxide (2 x 75 ml). The organic layer was dried over sodium sulphte filtered, and concentrated by ro'tary evaporation (700C, water aspirator). The resulting oil was dissolved in hot isopropyl alcohol and treated with fumaric acid'. Upon cooling, 2.38 g (27.4%) of pale brown crystals was collected, m.p. 161 162 C Analysis Calculated for C21H29N3O6 : C, 60.13 ; H, 6.96 ; N, 10.02 Found : C, 59.79 ; H, 6.93 ; N, 9.76 Example 51 2,3-Dihydro-4-methyl-2-[2-(2-methyl-1-pyrrolidinyl) ethyl]pyrido[3,2-f][1,4]oxazepin-5(4H)-one. To a solution of 3.5 g (0.0145 mole) of 2-(2-chloro ethyl)-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepine 5(4H)-one in ethanol (15 ml) was added 2-methyl pyrrolidine (5.0 g, 0.063 mole). The solution was heated to relfux for 3 hours with stirring. The ethanol was removed by rotary evaporation (water aspirator, 800C.). The residual oil was partitioned between dilute aqueous sodium hydroxide (56 ml) and chloroform (50 ml). The organic layer was saved and the aqueous layer extracted with chloroform (2 x 30 ml). All the chloroform layers were combined, dried over anhydrous sodium sulphate and concentrated by rotary evaporation (water aspirator, 700C.). The residual- oil was then distilled at 2000C. and low vacuum (vacuum pump) giving 1.5 g (35.7%) of a clear oil. Analysis : Calculated for C16H23N3O2 : C, 66.41 ; H, 8.01 ; N, 14.52 Found : C, 65.83 ; H, 8.06 ; N,14.39 Example 52 2,3-Dihydro-4-methyl-2-[2-(1H-pyrazol-1-yl)ethyl) pyrido [3,2-f][1,4]oxazepin-5(4H)-one. To a suspension of sodium hydride (1.2 g active, 0.05 mole) in dimethylformamide (15 ml) was added dropwise a solution of pyrazole (3.10 g, 0.045 mole) in diinethylformamide (15 ml). The resulting solution was then added to a solution of 2 - (2 -chloroethyl) '2 ,3-dihydro-4-methyl- pyrido [3,2-f][1,4] oxazepine-5(4H)-one (9.12 g, 0.038 mole) in 30 ml of dimethylformamide. The flask was sealed and stirred overnight. Because the reaction had not yet gone to completion at this point, pyrazole (3.12 g, 0.045 mole) was added t6 the reaction solution and stirred overnight. The reaction was still. not complete and another su'spension of sodium hydride . (0.5 g active, 0.021 mole) and pyrazole (1.5 g, 0.022 mole) in dimethylformamide (10 ml) was added and the reaction stirred overnight. the reaction appeared to be complete. Dimethylformamide was removed by rotaryevaporation (800C,. vacuum pump), and the residue taken up ïn chloroform (100 ml) which was washed with dilute aqueous sodium hydroxide (,1 x 50 ml), dried over aTydrous sodium sulphate and concentrated by rotary evaporation (70 C, water aspirator). . The material was purified by high pressure liquid chromatography, 95:5 by volume ethanol: methanol on a silica gel column. The fractions containing the desired product were concentrated by rotary evaporation (70 C, water aspirator0. Crystallization ensued upon cooling. The crystals were collected and recrystallized from ethanol. The yield was 1.5 (14.%), m,.p. 132-134 C. ' Analysis : Calculated for C14H18N4O2 : C, 61.75 ; H, 5.92 ; N,20.58 Found : C,61.35; E,5.89; N, 20.67 Example 53 2,3-Dihydro-2-[2-(1H-imidazol-1-yl)ethyl]-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one. To a solution of 2-(2-chloroethyl)-2,3-dihydro-4- methylpyrido [3,2-f][1,4]-oxazepine-5(4H)-one, 9.12 g (0?038 mole) in dimethylformamide (30 ml) was added imidazole, 5.66 g (0.083 mole). The solution was heated to 130 C. for 18 hr. Dimethylformamide was removed by rotary evaporation (80 C, vacuum pump) and the residue taken up in chloroform (100 ml). The chloroform was washed with dilute aqueous sodium hydroxide (30 ml), dried over sodium sulphate and concentrated by rotary evaporation (70 C, water aspirator) to an oil. Crystallization was induced with ethnol. White crystals, 1.5 g (14.5%) were collected, m.p. 150-152 C. Analysis : Calculated for C14H16N4O2 : C, 61.75 ; H, 5.92 ; N, 20.58 Found : C, 61.36 ; H, 5.92 ; N, 20.60 Example 54 2-r2-(D=nethylamino ) ethyll-4-ethyl-2, )-dihydropyrido [3,2-f][1,4]oxazepin-5(4H)-one oxalate [1:1]. To 36 ml of dimethylamine collected at 0 C. was added 6 g (0.021 mole) 2-(2-chloroethyl)-4-ethyl-2 ,3-dihydropyrido [3,2-f][1,4]oxazepin-5(4H)-one, hydrochloride. The flask was sealed tightly and stirred.70 hr at room temperature. The solution was then cooled to OOC. and the stopper of the flask removed. Dimethylamine was allowed to evaporate. The residue was taken up in chloroform (1 x 150 ml) and washed with dilute aqueous sodium hydroxide (1 x 50 ml). The organic layer was dried over sodium sulphate filtered and concentrated by rotary evaporation (700C, water aspirator). The residue was dissolved in hot isopropyl alcohol and treated with oxalic acid. Upon cooling, 4.5 (61.5 was, collected, m.p. 208 C. Analysis : Calculated for C16H23N3O6 : C, 54.38 ; H, 6.56 ; N, 11.89 Found : C,54.26; H, 6.61 ; N, 11.81 Example 55 2,3-Dihydro-4-ethyl-2-[2-(1-pyrrolidinyl)ethyl]pyrido [3,2-f][1,4]oxazepin-5(4H)-one oxalate [1:1]. 2-(2-Chloroethyl)-4-ethyl-2,3-dihydropyrido[3,2-f] El,4)oxazepin-5(4H)-one hydrochloride, 3 g (0.01 mole) was dissolved in pyrrolidine (30 ml) and heated to 70 C. for 30 minutes with, stirring. After cooling, the contents of the reaction flask were diluted with dilute aqueous sodium hydroxide (40 ml) and extracted with chloroform (2 x 30 ml). The chloroform layer was dried over sodium sulphate filtered and concentrated to a viscous brown oil by rotary evaporation (70 C, water aspirator). The 'oil was taken up in: hot isopropyl alcohol and treated with oxalic acid. Upon cooling, the resulting solid was recrystallized from isopropyl alcohol, giving pale brown crystals, 1.80 g (45.4%), m.p. 185-188 C. Analysis : Calculated for C18H25N3O6 : C, 56.98 ; H, 6.64 ; N, 11.07 Found : C, 56.90 ; H, 6.67 ; N, 10.90 Example 56 2,3-Dihydro-4-methyl-2-[2-(4-morpholinyl)ethyl]pyrido [3,2-f][1,4]oxazepin-5(4H)-thione. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepine-5(4H)-thione, 4.5 g (0.018 mole) was dissolved in morpholine (30 ml). The solution was heated with stirring to 500-600C. for 6 hr. The morpholine was then removed by rotary evaporation (900C, vacuum pump). The residue was taken up in chloroform (100 ml) and washed with dilute aqueous sodium hydroxide (2 x 30 ml). The organic layer was concentrated by rotary evaporation (60 C, water aspirator). The residue was recrvstallized from ethanol giving 3.26 g (60%) of light yellow crystals, m.p. 152-1530C. Analysis: Calculated for C15H21N3O2S : C,58.61; H,6.89 N, 13.66 Found : C, 58.48 ; H. 6.92 ; N, 13.62 Example 57 2-[2-(Dibutylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepïne-5(4H)-thione oxalate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido [3,2-f] [1,4]-oxazepine-5(4H)-thione, 4 g (0.016 mole) was suspended in di-n-butylamine (30 ml). Dimethylformamide (ca. 10 ml) was added to the stirred mixture until dissolution occurred. The solution was heated to 140 C. for 3.5 hr with stirring. Di-n-butylamine and dimethylformamide were removed by rotary evaporation (800C. vacuum pump).. The residue was then diluted with dilute aqueous sodium hydroxide (50 ml) and extracted with chloroform (3 x 40 ml). Chloroform was removed by rotary evaporation (70 C, water aspirator). The residue was dissolved in boiling isopropyl alcohol and treated with oxalic acid. Upon cooling, the resulting oxalate EXt was filtered and recrystallized from isopropyl alcohol to give' 3.2 g w (47%) of yellow crystals, m.p. 208 C. Analysis : Calculated for C21H33N3O5S : C, 57.38 ; H, 7.57 ; N, 9.56 Found : C,57.04; H,7.63; N,9.31 Example 58 2-[2-(Diethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepine-5(4H)-thione oxalate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methyl[3,2-f][1,4] oxazepine-5(4H)-thione, 4 g (0.016 mole) was suspended in diethylamine (30 ml). Dimethylformamide was added to the stirred suspension until dissolution occurred (10 ml). The stirred solution was heated to 65for for 8 hr. Diethylamine was removed by rotary evaporation (70 C, water aspirator); , the remaining dimethylformamide was removed at low pressure (vacuum pump) and 90 C. The residue was taken up in chloroform (100 ml) and washed with dilute aqueous sodium - hydroxide (2 x 30 ml). The organic layer was concentrated by rotary evaporation (700c, water aspirator). The residue was dissolved in boiling isopropyl alcohol and treated with oxalic acid. Upon cooling the oxalate salt, 1.7 g (28.5%) was obtained, m.p. 142-1440C. Analysis : Calculated for C17H25N3O5S : C, 53.25 ; H, 6.57 ; N, 10.95 Found : C, 53.14 ; H, 6.60 ; N, 10.72 Example 59 2,3-Dihydro-4-methyl-2-[2-(1-pyrrolidinyl)ethyl] pyrido[3,2-f][1,4]oxazepine-5(4H)-thione oxalate [1:1]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepine-5(4H)-thione, 5 g (0.02 mole) was dissolved in 30 ml of pyrrolidine. The solution was heated to 600-800C. for 35 minutes with stirring. After cooling to room temperature, the reaction mixture'was diluted with dilute aqueous sodium hydroxide (50 ml) and extracted with chloroform (2 x 50 ml). The organic layer was concentrated by rotary evaporation (70 c, water aspirator). Residual pyrrolidine was removed at 90 C. and vacuum pump. The residue was dissolved in hot-ethanol and treated with oxalic acid. Upon cooling, the oxalàte salt was collected and recrystallized twice from ethanol to give 3.35 g, (45% of product, m.p. 141 C. Analysis : Calculated for C17H23N2O5S : C, 53.53 ; H, 6.08 ; N, 11.02 Found : C, 53.39 ; H, 6.11 ; N, 10.91 Example 60 2,3-Dihydro-2-[2-(1H-imidazol-1-yl)ethyl]-4-methylpyrido-[3,2-f][1,4]oxazepine-5(4H)-thione oxalate [2:3]. To a solution of 2-(2-chloroethyl)-2,3-dihydro-4- methylpyrido[3,2-f][1,4]oxazepine-5(4H)-thione, 4.5 g (0.018 mole), in dimethylformamide (35 was addedimidazole (2.20 g, 0.638 mole). 'The resulting solution. was heated to 130 C. for 15 hrs. Dimethylformamide s7as removed by rotary evaporation (80 C, vacuum pump), and the residue diluted with dilu.te aqueous sodium hydroxide (50 ml). The aqueous solution was extracted with chloroform (1 x 50 ml), dried over anhydrous sodium sulphate and 'concentrated by rotary evaporation (water aspirator, 70 C); The resulting oil was treated with oxalic acid in ethanol. Four grams (54%) of pale yellow crystals were collected and recrystallized again With ethanol, m.p. 163-167 C. Analysis : Calculated for C17H19O7N4S : C, 48.22 ; H, 4.52 ; N, 13.23 Found : C, 48.04 ; H, 4.62 ; N, 13.18 Example 61 2-[2-(Dimethylamino)ethyl]-4-ethyl-2,3-dihydropyrido [3,2-f][1,4]oxazepin-5(4H)-thione. 2-(2-Chloroethyl)-4-ethyl-2,3-dihydropyrido[3,2-f] [1,4] oxazepin-5(4H)-thione hydrochloride, 5.00 g (0.016 mole) was added to 20 ml of anhydrous dimethylamine. The reaction flask was sealed tightly and stirred at room temperature for 6 days. The flask was opened after cooling to 0 C. and dimethylamine allowed to evaporate at room temperature. The residue was taken up in chloroform (100 ml) and washed with dilute, aqueous sodium hydroxide (1 x 30 ml). The chloroform layer was dried over sodium sulphate, filtered and concentrated by rotary evaporation. The residual oil was dissolved in hot cyclohexane. Upon cooling, 1.76 g (39.4s of light yellow crystals were collected, m.p. 73 C. Analysis : Calculated for C14H21N3OS : C, 60.18 ; H, 7.58 ; N, 15.03 Found : C, 60.32 ; H, 7.70 ; N,15.13 Exampe 62 2,3-Dihydro-4-methyl-2-[2-[methyl(phenylmethyl)amino) ethyl] pyrido [3,2-f][1,4]oxazepine-5(4H)-thione oxalate [1:1]. To a solution of 4 g (0.0155 mole) of 2-(2-chloro-. ethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine 5(4H)-thione in 70 ml of chloroform was added 10.0 g (o.o86 mole) of benzylmethylamine. The solution was stirred at reflux for 24 hr. The reaction solution was washed with water (2 x 50 ml). and concentrated by rotary evaporation (¯70 C, water aspirator). The residue was distilled on a molecular still at 1650C./0.l mm. The residue was treated with oxalic acid in hot isopropyl alcohol. Upon cooling, two crops of crystals were collected. The purity of each crop was checked. The two crops were combined and recrystallized together in hot isopropyl alcohol. Upon cooling 3.69 g (55)g) of pale yellow crystals, m.p. 163-1660C were collected. Analysis: Calculated for C21H25N3O5S : C,58.45; H,5.84; N, 9.74 Found : C, 58.24 ; H, 5.92 ; N, 9.61 Example 63 2,3-Dihydro-2-[2-(methylamino)ethyl)-4-methylpyrido [3,2-f][1,4]oxazepine-5(4H)-thione oxalate [1:1.5]. 2-(2-Chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepine-5(4H)-thione, 4.0 g (0.016 mole) was suspended in a 30% solution of methylamine in 70 ml of ethanol and allowed to stir for 56 hr at room temperature. Because of incomplete reaction, the reaction solution was heated slowly over a 2 hr period to 55 C. and stirred at that temperature- for 24 ,hr. Methylamine was removed by water aspiration for 1.5 hr. The resulting solution was concentrated by rotary evaporation (700C, water-aspirator). The residual o,il was taken up in chloroform (150 ml) and washed with 2, X aqueous potassium hydroxide (2 x 50 ml). The chloroform layer was dried over sodium sulphate and concentrated by rotary evaporation (70 C, water aspirator). The residue was dissolved in hot ethanol and- treated with oxalic acid. Upon cooling, 2.0 g (37.5%) of yellow crystals were collected, m.p. 137-1380C.' Analysis : Calculated for C15H20N3O7S : C, 46.63 ; H, 5.22 ; N, 10 Found : C, 46.47 ; H, 5.35 ; N, 10.85 Example 64 7-Chloro-2,3-dihydro-4-methyl-2-[2-[1-pyrrolidino) ethyl)pyrido[3,2-f][1,4]oxazepin-5(4H)-one fumarate [1:2.5] 7-Chloro-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)-one (2.5 g, 0.009 mole) was, dissoslved in 50 ml pyrrolidine and the solution was heated to 80 C. for 1 hr. The pyrrolidine was removed by rotary evaporation (80 C., water aspirator) and the residue dissolved in 100 ml of chloroform. The organic layer was washed with water (2 X 50 ml), dried over sodium sulphate and concentrated by rotary evaporation (¯80 C., water aspirator). The residue was treated with fumaric acid and allowed to stand overnight. The resulting crystals were collected, 1.25 g (23.2%), m.p. 164-166 C. Analysis : Calculated for C25H30N3O12Cl : C, 50.05 ; H, 5.04 ; N, 7.00 Found : C, 50.22 ; H, 5.14 ; N,7.02 Example 65 7-Chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4 methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one oxalate (1:1). . A 2.8 g (0.01 mole) sample of 7-chloro-2-(2-chloro- ethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H) one was added to 25 ml of dimethylamine and stirred for -96 hr in a sealed flask. The excess amine was allowed tot evaporate and the residue was partitioned between chloroform and dilute sodium hydroxide. The chloroform was dried over sodium sulphate and concentrated. The residue was treated with 0.7 g of oxalic acid in isopropyl alcohol. The resulting crystals were recrystallized from the same solvent. Yield was 1.5 g of oxalate salt (400, m.p. 150-1560C. Analysis: Calculated for C15H2ON3O6Cl : C,48.20; H,5.39;' N, 11.24 Found : c,48.og, H, 5.47 N, 11.12 Example 66 4-Cyclohexyl-2-[(dimethylamino)methyl]-2,3-dihydro pyrido[3,2-f][1,4]oxazepin-5(4H)-one oxalate. Utilizing the procedure of Example 10, 2-(chloromethyl)-4-cyclohexyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin 5(4H)-one (Intermediate 35) is reacted.with 40% aqueous dimethylamine and reacted with oxalic acid in isopropyl alcohol. Example 67 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4-phenylmethylpyrido[3,2-f][1,4]oxazepin-5(4H)-one oxalate [1:1.5] hemihydrate. A solution containing 94.2 g (0.6 mole) of 2 chloronicotinic acid and 100 g (0.54 mole) of 1-ben:zyl-3- pyrrolidinol in 800 ml of dry tetrahydrofuran was added at a rapid drop to a stirred suspension of 52 g (1.3 mole) of 60% sodium hydride/mineral oil in 500 ml of dry tetrahydrofuran at reflux temperature (addition time was about 1 hr). The mixture was heated to reflux for an additional 1.5 hr and then cooled to room temperature. Approximately 1 liS of ethyl acetate was added and filtration attempted unsuccessfully. The mixture was allowed to stand overnight at room temperature and then was concentrated on the rotary evaporator at 100 C. and 50 mm pressure The residue was dissolved in 1 litre of chloroform and the pH of the solution was adjusted to 6.15-w',ith hydrogen chloride gas. To the solution-was added, with stirring, 383 g (-1.0 mole of triphenylphosphine and 383 g (2.48 moie) of carbon tetrachloride. The mixture was refluxed - for 1 hr and 50 ml of ethanol was added The solution was cooled to room temperature and extracted three times, with 400 ml portions of dilute hydrochloric acid. The chloroform layer was extracted with dilute sodium hydroxide, dried over sodium sulphate and concentrated. The mass spectra indicated the presence of 2,- (2 -chloroethyl) -2 , 3-dihydro-4 - (phenylmethyl) pyrido[3,2-f][1,4]oxazepin-5(4H)-one (mass 316), triphenylphosphine (mass 262) and triphenylphosphine oxide (mass 278). One-third of the residue was chromatographed on a high pressure liquid chromatopraph in an unsuccessful attempt to purify the compound. The other 2/3 of the residue was dissolved in 30 ml of chloroform and added to a solution of 30 g of dimethyl amine in ethanol. The solution was heated to reflux for 4 hr and concentrated on the rotary evaporator. The residue was partitioned between chloroform and I N hydrochloric acid. The acid layer was made basic with sodium hydroxide and extracted with chloroform-. The chloroform layer was dried over sodium sulphate and concentrated. The residue (10 g) was treated with an ettuivalent amount of oxalic acid in a mixture of isopropyl alcohol ethanol-isopropyl ether. The resulting crystals in the amount of 9 g (5%) were recrystallized from the same solven mixture, m.p. 95-98 C. Analysis : Calculated for C44H54N6O17 : C, 56.28 ; H, 5.79 ; N, 8.95 Found : C, 56.61 ; H, 5.76 ; N, 8.77 Example 68 2-[2-(Dimethylamino)ethyl]-2,3-dihydropyrido[3,2-f] [1,4]oxazepin-5(4H)-one. A solution of- 3.0 g (0.006 mole) of 2-(2-(dimethyl- amino ethyl]-2,3-dihydro-4-phenylmethylpyrido[3,2-f][1,4] oxazepin-5(4H)-one oxalate [1:1.5]-hemihydrate in bout 50 ml of water was made basic with dilute aqueous sodium hydroxide solution and then extracted with three - ml portions of -benzene. The combined.benzene extract was dried over anhydrous sodium sulphate and concentrated on the rotary evaporator (steam bath/50 mm). The residue was dried further by azeotroping 2 times with about 50 ml of dry benzene, evaporating to dryness each time. The final residue was dissolved in 40 ml of liquid ammonia and .' small spheres of sodium.were added with stirring to the solution until a blue color persisted for 20 minutes. (Addition time was about 1 hr). Three grams of ammonium: . chloride was added slowly and the ammonia was allowed to. evaporate. The residue was suspended in chloroform and - - - the mixture was filtered. The filtrate was concentrated and the residu'e chromatographed on preparative high pressure liquid chromatograph using a silica gel column and eluting with 75% ethyl acetate / 25% dimethylformamide. the yield of product was 0.1 g (7%). The chemical ionization mass spectrophotometer gave a peak at 236 corresponding to a molecular weight of 235. The ÚH NMR spectrum of the of the subject compound was obtained in CDCl3 containing 1% tetramethylsilane (TMS) and is consistent with the proposed, structure and dimethylformamide (DMF) and mineral oil as minor impurities. The chemical shifts, multiplicities, and assignments are given below: EMI106.1 Chemical Shifts (multiplicities) Assignments 8.45 (multiplet) H(8) and H(6) 8.00 (singlet) C-H (DMF) 7.85 (broad singlet) N-H 7.20 (doublet of doublets) H(7) 4.65 (pentet) H(2) 4.05 (broad singlet) unknown impurity 3.50 (triplet) H2 (3) 2.95 (singlet) CH3(DMF) 2.90 (singlet) CH3(DMF) 2.60 (triplet) H2-&alpha;to amino nitrogen 2.25 (singlet) N(CH3)2 2.05 (multiplet) H2-ss to amino nitrogen 0.7-1.7 (multiplet) mineral oil Example 69 2-[3-(Dimethylamino)propyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepin-5(4H)-one fumarate [1:1.5] hemihydrate. To 5.0 g (0.021 mole) of 2-(3-aminopropyl)-2,3-dihydro 4-methylpyrido[3,2-f][1,4]-oxazepin-5(4H)-one was added, while cooling in -a water bath, an 88 aqueous solution of formic' acid, 20 g (0.38 mole). To the resulting solution was added a solution of 37% aqueous formaldehyde (inhibited with 13% methanol), 10.7 g (0.15 mole). The resulting. solution was heated on a steam bath for 5.5 hr. The mixture was cooled and 100 ml of dilute aqueous hydrochloric acid was added. The solution was evaporated to dryness and the residue was dissolved in 50 ml of water. The solution was neutralized with dilute aqueous potassium hydroxide and ' extracted with four 50 ml portions of chloroform. The combined chloroform extracts was dried over sodium sulphate and concentrated by rotary evaporation. The residue was reacted with fumaric acid in hot isopropyl alcohol. 'The collected product, 3.0 g (31.8%) was recrystallized twice from isopropyl alcohol, m.p. 108-1100C. Analysis : Calculated for C40H56H6O17 : C, 53.81 ; H, 6.32 N, 9.41 Found : C, 53.69 ; H, 6.33 ; N, 9.41 Example 70 . 2-[3-(Dimethylamino)propyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]oxazepine-5(4H)-thione oxalate [1:2]. To a solution of 11.0 g (0.042 mole) of 2-[3-(dimethyl amino)propyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5(4H)-one in 125 ml of pyridine was added 9.25 g (0.042 mole) of phosphorus pentasulphide i, The mixture was heated to reflux for 3.5 hr while stirring. After cooling to room temperature, the reaction solution was added to an equal volume of 2 molar potassium hydroxide. The mixture-was extracted with 800 ml of methylene chloride in several ..portions. The organic phase was washed with three 100 ml portions of dilute potassium hydroxide, dried over, sodium sulphate, filtered and concentrated by rotary evaporator -(water-aspirator, 70 C.). The residual oil was subjected to reduced pressure of the vacuum pump for 2 hr at 900C. and then cooled and reacted with oxalic acid in isopropyl alcohol. Two crops, a.5 and 3.1 g were collected, combined and recrystallized from isopropyl alcohol . to give 6.5 g (34%) of yellow crystals, m.p. 136-1380C. Analysis : Calculated for C18H25N3O9S : C, 47.05 ; H, 5.42 N,9.16 Found : C, 46.76 ; H, 5.75 : N, 9.04 Example 71 7-Chloro-2-[2-(dimethylamino)ethyl)-2,3-dihydro-4methylpyrido[3,2-f][1,4]oxazepine-5(4H)-thione fumarate [1:1] hemihydrate, hemiisopropyl alcoholate. To 55 ml of a methanolic solution containing 57% by volume dimethylamine was added 2.50 g (0.009 mole) of 7-chloro-2 -(2 -chloroethyl) -2, 3-dihydro-4-me thylpyrido [3,2-f][1,4]-oxazepine-5(4H)-thione. The reaction vessel was sealed and allowed to stand for 16 hr. Thin-layer chromatography indicated the reaction was about 60% complete. The solution was heated gradually to 45 C. (heating time about 5 hr). Methanol and unreacted dimethylamine were removed by rotary evaporator (water aspirator, 6o0c.). The residue was taken up in 100 ml of chloroform and the solution was washed with, two 40 ml portions of water. The organic layer was dried over sodium suphate. filtered and concentrated by rotary evaporator. The residue was reacted with fumaric acid in isopropyl alcohol. The resulting crystals, l.43 g (36.5%) were recrystallized from isopropyl alcohol and dried thoroughly in a drying pistol, m.p. 98-1040C. Analysis : Calculated for C37H54N6O12Cl2S2 : C, 48.84 ; H, 5.98 ; N, 9.23 Found : C, 48.82 ; H, 5.80 ; N, 9.37 Table 1 EMI108.1 Intermediate No. A(Y)0-2 B R E X n Salt 1 - benz 0 -CH3 O Cl 2 2 benz 0 -CH2-C6H5 0 Cl 2 3 naphth[2,3-f] 0 -CH3 0 Cl 2 4 pyrido[3,2-f] 0 -CH3 0 Cl 2 HCl 5 8-Cl-benz 0 -CH3 0 Cl 2 6 7-Br-benz 0 -CH3 0 Cl 2 7 7-Cl-benz O -CH3 O Cl 2 8 naphth[2,1-f] 0 -CH3 0 Cl 2 9 7-OCH3-benz 0 -CH3 0 Cl 2 10 benz S -CH3 0 CI 2 11 Pyrido[3,2-f] S -CH3 0 Cl 2 12 naphth[2,3-f] S -CH3 0 Cl 2 13 8-Cl-benz S -CH3 0 Cl 2 14 7-Br-benz S -CH3 0 Cl 2 15 naphth[2,1-f] S -CH3 0 Cl 2 16 pyrido[4,3-f] 0 -CH3 0 Cl 2 HCl 17 pyrido[3,4-f] 0 -CH3 0 Cl 2 HCl 18 pyrido[2,3-f] 0 -CH3 0 Cl 2 HCl 19 7-Cl-benz S -CH3 0 Cl 2 20 7,9-diiodo-benz 0 -CH3 0 Cl 2 21 pyrido[3,2-f] S -CH3 0 Cl 1 HCl 22 pyrido[4,3-f] S -CH3 0 Cl 2 23 7-OCH3-bnez S -CH3 0 Cl 2 24a) benz 0 -C5H11 0 Cl 2 b) benz 0 -C2H5 0 Cl 2 c) benz 0 -CH(CH3)2 0 Cl 2 d) benz 0 4-Cl-C6H4-CH2- 0 Cl 2 e benz 0 4-CH3-C6H4-CH2- O Cl 2 - f) benz 0 3,5-(OCH3)2- 0 Cl 2 C6H -CH2 g) benz 0 3-CF3-C6H4-CH2- 0 Cl 2 h) benz 0 4-NO2-C6H4-CH2- 0 Cl 2 25a) pyrido[3,2-f] 0 -C6H11 0 Cl 2 HCl b) pyrido[3,2-f] 0 -C2H5 0 Cl 2 HCl c) pyrido[3,2-f] 0 -CH(CH3)2 0 Cl 2 HCl d) pyrido[3,2-f] 0 4-Cl-C6H4-CH2- 0 Cl 2 HCl e) pyrido[3,2-f] 0 4-CH3-C6H4-CH2-0 Cl 2 HCl f) pyrido[3,2-f] 0 3,5-(OCH3)2- 0 Cl 2 HCl C6H - CH2 g) pyrido[3,2-f] 0 3-CF3-C6H4-CH2- 0 Cl 2 HCl h) pyrido[3,2-f] 0 4-NO2-C6H4-CH2- 0 Cl 2 HCl 26 pyrido[3,2-f] 0 -CH3 S Cl 2 27 pyrido[3,2-f] S -CH3 S Cl 2 Table 1 cont. Intermediate No. A(Y)0-2 B R E X n Salt ' 28 pyrido[3,4-f] 0 -CH3 0 Cl 2 29 pyrido[3,4-f] S -CH3 0 Cl 2 HCl 30 pyrido[3,2-f] 0 -CH3 0 -CN 2 31 pyrido[3,2-f] 0 -C2H5 0 Cl 2 HCl 32 pyrido[3,2-f] S -C2H5 0 Cl 2 HCl 33 7-Cl-pyrido 0 -CH3 0 Cl 2 [3,2-f] 34 7-Cl-pyrido S -CH3 0 Cl 2 [3,2-f] 35 pyrido[3,2-f] 0 -C6H11 0 Cl 1 36 pyrido[3,2-f] 0 -CH2C6H5 0 Cl 2 - Table 2 EMI111.1 EMI111.2 <tb> No. <SEP> ¯¯¯¯¯¯¯¯ <SEP> A(Y)d-3 <SEP> 1 <SEP> n <SEP> B.lt <tb> 1 <SEP> ban: <SEP> 0 <SEP> -Ha <SEP> 0 <SEP> -N <SEP> CS, <SEP> a <SEP> 2 <SEP> xci <tb> 2 <SEP> benz <SEP> 0 <SEP> CS- <SEP> 0 <SEP> -1 <SEP> -tl(Cg, <SEP> ). <SEP> 2 <tb> buu <SEP> 0 <SEP> CS- <SEP> 0 <SEP> 0 <SEP> 2 <SEP> prate <tb> 4 <SEP> benz, <SEP> 0 <SEP> -CS, <SEP> 0 <SEP> -N <SEP> 2 <SEP> <tb> ban: <SEP> 0 <SEP> % <SEP> 0 <SEP> CS, <SEP> 2 <SEP> furate <tb> benz <SEP> B <SEP> , <SEP> 0 <SEP> X <SEP> CS, <SEP> a' <SEP> 2 <SEP> HC1 <tb> 7 <SEP> benz <SEP> 0 <SEP> -crtd <SEP> C <SEP> -x <SEP> CS,, <SEP> 2 <SEP> 2 <SEP> 5,0 <tb> 8 <SEP> ban:' <SEP> B <SEP> -CE, <SEP> 0 <SEP> O <SEP> 2 <tb> 9 <SEP> phtb <SEP> 2,3-f <SEP> 0 <SEP> -CS, <SEP> 0 <SEP> -QII <SEP> o <SEP> 2 <SEP> oxalata <tb> 10 <SEP> pyrido <SEP> 32-f <SEP> 0 <SEP> "'CS,' <SEP> 0 <SEP> - <SEP> CS,, <SEP> 2 <SEP> 1.5 <SEP> tnarite <tb> 11 <SEP> pyrido <SEP> 3,2-f <SEP> S <SEP> -Cs, <SEP> - <SEP> 0 <SEP> - <SEP> CS, <SEP> a, <SEP> 2 <SEP> ftmarate, <tb> <SEP> -' <SEP> 0.5- <SEP> et)Lno1 <tb> 12. <SEP> - <SEP> Pyrioo±3,2-f) <SEP> - <SEP> S <SEP> -CE, <SEP> -CS,), <SEP> 2 <SEP> ¯ <tb> 13 <SEP> ban: <SEP> S <SEP> -QII <SEP> a <SEP> 0 <SEP> 4 <SEP> 0 <SEP> 2 <SEP> <tb> 14 <SEP> benz <SEP> 0 <SEP> -CE, <SEP> 0 <SEP> .HCBa <SEP> 2 <SEP> .2unte, <tb> 15 <SEP> ban: <SEP> - <SEP> 0 <SEP> .-CE, <SEP> 0 <SEP> '- <SEP> 2 <SEP> <tb> 16 <SEP> benz <SEP> S <SEP> -CE, <SEP> 0 <SEP> -H <SEP> 2 <SEP> <tb> 17 <SEP> benz <SEP> 5 <SEP> -CE,. <SEP> 0 <SEP> 2 <SEP> <tb> 18 <SEP> Sd-benz <SEP> 5 <SEP> -CE, <SEP> 0 <SEP> -J <SEP> CS' <SEP> a <SEP> 2 <SEP> Sci <tb> 19 <SEP> 1-b'nz <SEP> 0 <SEP> -CE, <SEP> 0 <SEP> - <SEP> CS, <SEP> t <SEP> 2 <SEP> oxalato <tb> 20 <SEP> 'I-Br-buu <SEP> 0 <SEP> -CE, <SEP> 0 <SEP> - <SEP> CS, <SEP> a <SEP> 2 <SEP> oxalate <tb> 21 <SEP> naph2,1-f) <SEP> 0 <SEP> -CE, <SEP> 0 <SEP> - & CE, <SEP> i <SEP> 2 <SEP> oxalate <tb> 22 <SEP> a <SEP> PiOJI,ff <SEP> 0 <SEP> -CE, <SEP> 0 <SEP> - <SEP> CS, <SEP> a <SEP> 2 <SEP> fumarate <tb> <SEP> C <SEP> pido <SEP> -CE <SEP> O <SEP> CR, <SEP> a <SEP> -EI( <SEP> Cgr <SEP> 2 <SEP> twrate <tb> 2',3-'-f <SEP> 0: <SEP> NJ <SEP> CS' <SEP> a <SEP> -HICEt,f <SEP> 2 <SEP> .5 <SEP> acl <tb> 23 <SEP> pyrido <SEP> 4,3-f) <SEP> 0 <SEP> -1 <SEP> o <SEP> -sloE4 <SEP> 1 <SEP> CS, <tb> 25 <SEP> nphth2, <SEP> J-fj <SEP> : <SEP> -CB, <SEP> 2 <SEP> oxalate, <tb> <SEP> -CE, <SEP> 0 <SEP> - <SEP> CSa <tb> <SEP> 1,2 <SEP> 5,0 <tb> 26 <SEP> 7,9 <SEP> diiobenz <SEP> 0 <SEP> -CE, <SEP> - <SEP> 0 <SEP> - <SEP> CS, <SEP> a <SEP> 2 <SEP> <tb> 2 <SEP> 7-C <SEP> 1-benz <SEP> 0 <SEP> -CS, <SEP> - <SEP> a <SEP> -x <SEP> Ccs,Sa: <SEP> 2 <SEP> oxilate <tb> 2 <SEP> pyrido <SEP> 3,2-f <SEP> 0 <SEP> -CE, <SEP> -- <SEP> 0 <SEP> -N <SEP> cBS <SEP> 1 <SEP> -' <SEP> <tb> 29 <SEP> pyrido <SEP> 3,2-f <SEP> 5 <SEP> '-CE, <SEP> - <SEP> 0 <SEP> -N <SEP> CS, <SEP> ( <SEP> ethjod'jde <SEP> <tb> 30 <SEP> 7-C1-brar <SEP> I <SEP> -CE, <SEP> 0 <SEP> -N <SEP> CS, <SEP> 2 <SEP> oxaUte.l0 <tb> 3321 <SEP> b' <SEP> Pphth[P, <SEP> lf <SEP> I <SEP> I <SEP> - <SEP> :: <SEP> '-:Nx.:,:: <SEP> j <tb> 33 <SEP> 7,-ban: <SEP> 0 <SEP> 0 <SEP> -CE, <SEP> -N <SEP> CS, <SEP> 2 <SEP> oxalate' <tb> 'I-ar-anr <SEP> I.-crt <SEP> a <SEP> -x <SEP> CS, <SEP> a <SEP> 2 <SEP> cxi <SEP> 1ate.0 <tb> 35 <SEP> a <SEP> benz <SEP> 0 <SEP> -Cii <SEP> 0 <SEP> -M <SEP> CE, <SEP> a <SEP> 2 <SEP> oxalate <tb> <SEP> b <SEP> ban: <SEP> 0 <SEP> -C,S, <SEP> 0 <SEP> -'N <SEP> CE, <SEP> a <SEP> oxalate <tb> <SEP> C <SEP> ban: <SEP> 0 <SEP> -CE(Cs,), <SEP> 0 <SEP> -N <SEP> CS <SEP> 2 <SEP> 11:t: <tb> <SEP> d <SEP> ban: <SEP> - <SEP> 0 <SEP> 4-c- <SEP> 0 <SEP> -P\CEIII <SEP> - <SEP> CS, <tb> Table 2 (cont.) EMI112.1 <tb> <SEP> 2 <SEP> N <SEP> tz0 <SEP> oxalat. <tb> <SEP> : <SEP> npr <SEP> <SEP> 35-toCS <SEP> - <SEP> O <SEP> * <SEP> cs <SEP> 2 <SEP> oxilate <tb> <SEP> ben: <SEP> krr+ <SEP> '0 <SEP> -x,cs: <SEP> ' <SEP> 2 <SEP> oxilato <tb> <SEP> ben: <SEP> O <SEP> . <SEP> CJ4CE1- <SEP> 0 <SEP> -X5U)s <SEP> 2 <SEP> oxalat. <tb> )6 <SEP> 3,2-b <SEP> 0 <SEP> '-CeN,: <SEP> 0 <SEP> - <SEP> O. <SEP> 4 <SEP> Cur, <SEP> a <SEP> 2 <SEP> fo2orata <SEP> <tb> <SEP> L <SEP> pyrido <SEP> 3,2-f <SEP> <SEP> 4zs <SEP> O <SEP> -K <SEP> CR, <SEP> X <SEP> 2 <SEP> Salt <tb> <SEP> c <SEP> pyrt6o <SEP> 312-f <SEP> 0 <SEP> c$(cza}s <SEP> O' <SEP> -x <SEP> CR3 <SEP> a <SEP> 2 <SEP> turnta <tb> <SEP> a <SEP> pyrido <SEP> ),2-S <SEP> 0 <SEP> 4ai-. <SEP> 0 <SEP> -x <SEP> =, <SEP> X <SEP> 2 <SEP> fLirat. <tb> <SEP> C <SEP> pyrido <SEP> 3,2-f <SEP> 0 <SEP> 4"'CR,-CH4C- <SEP> o <SEP> O <SEP> -X; <SEP> CR, <SEP> t <SEP> 2 <SEP> fsrata <tb> <SEP> f <SEP> pyrido <SEP> 3,2-f <SEP> O <SEP> ss <SEP> 4Ci- <SEP> O <SEP> - <SEP> C, <SEP> a <SEP> 2 <SEP> hrmPrtr <tb> <SEP> S <SEP> pyrido <SEP> 3,2-f <SEP> 0 <SEP> s <SEP> XCEE- <SEP> O <SEP> -X <SEP> c8 <SEP> | <SEP> <SEP> 2 <SEP> fu=trnt. <tb> <SEP> h <SEP> p <SEP> o <SEP> 3,2-f <SEP> -o <SEP> 4ffi= <SEP> 4c8X- <SEP> 1 <SEP> 4 <SEP> ch <SEP> a <SEP> 2 <SEP> Srate <tb> 3T <SEP> ;) <SEP> ban: <SEP> O <SEP> O <SEP> 4 <SEP> 0 <SEP> l-pyrrol±dinyl <SEP> 2 <SEP> farate <tb> <SEP> b) <SEP> benz <SEP> O <SEP> -'CR, <SEP> 0 <SEP> 1-pipiridinyl <SEP> 2 <SEP> fi2oratt <tb> <SEP> c) <SEP> benz <SEP> O <SEP> "'CR, <SEP> 0 <SEP> r-pipcrIfnyl <SEP> 2 <SEP> funrstz <tb> <SEP> d) <SEP> ton: <SEP> O <SEP> ice, <SEP> O <SEP> "'CR,-piptri- <SEP> 2 <SEP> fussrate <tb> <SEP> vinyl <tb> 38 <SEP> M t5w2-f <SEP> 3 <SEP> 0 <SEP> -'CR, <SEP> 5 <SEP> -x(cs,)a <SEP> 2 <SEP> 2 <SEP> 2IC1 <SEP> - <tb> 39 <SEP> 'Prrt"o±3,2-f) <SEP> 8 <SEP> -'CR, <SEP> b <SEP> 4Cii)L <SEP> 2 <SEP> oxaUte <tb> PyridoE3,'I-f) <SEP> O <SEP> -'CR,, <SEP> O <SEP> ;wei$)2 <SEP> 2 <SEP> 1/2 <SEP> EeO <SEP> - <SEP> <tb> <SEP> 2 <SEP> oxalate <tb> 41 <SEP> pysidor3,4 <SEP> S <SEP> -'CR, <SEP> O <SEP> <SEP> )2 <SEP> 2 <SEP> 2 <SEP> oxa1it,: :." <tb> 42 <SEP> pyrido <SEP> 3,2-f <SEP> 0 <SEP> -'CR, <SEP> 0 <SEP> s <SEP> 3 <SEP> 102 <SEP> iE20 <SEP> o <tb> <SEP> oxalate <tb> 43 <SEP> - <SEP> pyridot3,2-fz <SEP> 0 <SEP> -'CR, <SEP> O <SEP> -P <SEP> 0 <SEP> 2 <SEP> taleate <tb> <SEP> pyridor,2-f <SEP> Oo <SEP> l-pyrrolidinyl <SEP> 22 <SEP> fumarate <tb> ii <SEP> ido <SEP> 3,2-f) <SEP> 0 <SEP> -Cg, <SEP> O <SEP> lYrlid1inY1 <tb> A <SEP> pidc(3, <SEP> 2-f <SEP> -'CR, <SEP> <SEP> a <SEP> O <SEP> -tt(Ctz5)2 <SEP> 2 <SEP> oxalate <tb> 47 <SEP> pyridot3,2-f) <SEP> 0 <SEP> -cR <SEP> o <SEP> l-piperiasnyl <SEP> 2 <SEP> oxalate <tb> 48 <SEP> pyrido <SEP> 3,2-f) <SEP> Ck <SEP> -CS, <SEP> o <SEP> -NcN, <SEP> (enzyi) <SEP> 2 <SEP> maSeate <tb> 49 <SEP> pyrido3, <SEP> 2-fi <SEP> 0 <SEP> -CH3 <SEP> O <SEP> -JCH, <SEP> -ceSe <SEP> 2 <SEP> <tb> 50 <SEP> pyridc(3,2-f) <SEP> 0 <SEP> -CR, <SEP> O <SEP> c5 <SEP> 2 <SEP> , <SEP> fumarate <tb> <SEP> 7 <tb> 51 <SEP> pyridor,3,2-f) <SEP> 0 <SEP> -'CR, <SEP> o <SEP> o2 <tb> 52 <SEP> Pyrido(3,2,-f) <SEP> 0 <SEP> -Cza <SEP> O <SEP> cW <SEP> 2 <tb> 53 <SEP> PyridoE3,2.-f) <SEP> 0 <SEP> -ca, <SEP> <SEP> - <SEP> 2 <SEP> 2 <tb> <SEP> 'V <tb> 55 <SEP> pysidol3,2-i <SEP> 0 <SEP> ¯Cwi3s <SEP> - <SEP> <SEP> O <SEP> N(Cs,)a <SEP> 2 <SEP> oxalate <tb> 55 <SEP> Pyrido±3,2-f) <SEP> i <SEP> D <SEP> - <SEP> --CtE4 <SEP> O <SEP> <SEP> l-pyrrolidinyl <SEP> 2 <SEP> oxalate <tb> 56 <SEP> - <SEP> Pyrido±3,2-f) <SEP> S <SEP> -CR, <SEP> <SEP> fn <SEP> 2 <SEP> <tb> <SEP> -aT <SEP> O <tb> ;yrido <SEP> 3,2-15 <SEP> o <SEP> -'CR, <SEP> 0 <SEP> -J <SEP> n-butyl)1 <SEP> 2 <SEP> oxalite <tb> 55 <SEP> tys4 <SEP> dot3,2-±: <SEP> S <SEP> -CS, <SEP> 0 <SEP> -N <SEP> 5 <SEP> )z <SEP> 2 <SEP> oxilite <tb> 19 <SEP> pyrido[,2-ij <SEP> ss <SEP> - <SEP> -CR, <SEP> 0 <SEP> l-pyrrolidinyl <SEP> 2 <SEP> oxalxte <tb> 60 <SEP> pyr$bot3,2-S) <SEP> s <SEP> w <SEP> O <SEP> in <SEP> -\ <SEP> 2 <SEP> 1.5 <SEP> oxxlzte <tb> Table 2 (cont.) 61 pyrido[3,2-f] S -C@H@ 0 -N(CH3)2 2 62 pyrido[3,2-f] S -CH3 0 -N(CH3)(benzyl) 2 oxalate 63 pyrido[3,2-f] S -CH3 0 -NHCH3 2 1.5 oxalate 64 7-Cl-pyrido 0 -CH3 0 -1-pyrrolidinyl 2 2.5 fumarate [3,2-f] 65 7-Cl-pyrido 0 -CH3 0 -N(CH3)2 2 oxalate [3,2-f] 66 pyrido[3,2-f] 0 -C6H11 0 -N(CH3)2 1 oxalate 67 pyrido[3,2-f] 0 -CH@C@H5 0 -N(CH3)2 2 1.5 oxalate, 1/2 H2O 68 pyrido[3,2-f] 0 H 0 -N(CH3)2 2 69 pyrido[3,2-f] 0 -CH3 0 -N(CH3)2 3 1.5 fumarate, 0.5 H2O 70 pyrido[3,2-f] S -CH3 0 -N(CH3)2 3 2 oxalate 71 7-Cl-pyrido S -CH3 0 -N(CH3)2 2 1/2 H2O, [3,2-f] 1/2 (CH3)2 HOH Pharmaceutical Compositions The invention further provides pharmaceutical compositions for administration to.a living animal body comprising, as active ingredients, at least one of. the compounds of Formula I according to the invention in association with a pharmadeutical carrier or excipient. The compounds are thus presented in a therapeutic composition suitable for oral, rectal, parenteral, subcutaneous, intramuscular, intraperitoneal, intravenous, or nntranasal administratron. Thus, for example, compositions for oral administration can take the form of elixirs, capsules, tablets or coated tablets containing carriers conveniently used in the pharmaceutical art. Suitable tableting excipients include lactose, potato and maize starches, talc, gelatin and stearic and silicic acids, magnesium stearate and polyvinyl pyrrolidone For parenteral- administratid - the carrier or excipient can be comprÅased of a sterile parenterally acceptable liquid; e.g., water or arachis oil contained in ampoules. In compositions for rectal administration, the. carrier can be comprised -of.a suppository base; e.g., cocoa butter or a glyceride. Application to the nose, throat or bronchial region can be in the form of gargle or an aerosol spray containing small particles of the agent of Formula I in a spray or dry powder form. Advantageously, the compositions are formulated as dosage units, each unit being adapted two supply a fixed: dose of active ingredients. Tablets, coated tablets, capsules, ampoules and suppositories are examples of - t preferred dosage forms according to the invention, It is only necessary that the active ingredient constitute an effective amount; i.e.i such that a suitable effective dosage will be consistent with the dosage form employed. The exact individual dosages, as well as daily dosages, will of course be determined according to standard medical principles under the direction of a physician or veterinarian. Generally, the pharmacology tests on guinea pigs in comparison to certain other antihistaminic drugs suggests an effective dose for an adult will be in the range of 2 to -8 mg-for the more active compounds. Based on the animal data, unit dosages containing an amount of compound equivalent to about. 0.03 to 0.10 mg of active drug per, kilogram of, boidy weight are contemplated Daily dosages of about 0.2,to 0.6 mgAg of body weight are contemplated for humans and obviously several small unit dosage forms may be administered at one time. 'However the scope of the invention is not to be limited by these contemplations due to uncertainty in transposing from animal data to humans. Examples of unit dosage compositions are as follows: .Capsules= Ingredients Per capsule 1. Active ingredient @@ 4 mg. 2. Lactose 150 mg. 3. Magnesium stearate 4 mg. tablets: Ingredients 1. Active ingredient 4 mg. 2. Corn starch 20 mg. 3. Kelacid 20 mg. 4. Keltose 20 mg. 5. Magnesium stearate 1.3 mg. Procedure for tablets: 1. Blend 1, 2, 3, 4 in larger amounts. 2. Add sufficient water portionwise to blend to the blend from step 1 with careful stirring after each addition. Such additions of water. and stirring continue until the mass is of a constituency to permit its conversion to wet granules. 3. The wet mass is converted to granules by, passing it through the oscillating granulator using 8 mesh screen. 4. The wet granules are then dried in an oven at 1400F (600C). 5. The dry granules are lubricated with the magnesium stearate. 6. The lubricated granules are compressed on a suitable tablet press. Intramuscular Injection Per ml. 1. Active ingredients 10.0 mg. 2. Isotonic buffer solution 4.0 q.s to 1.0 ml. Procedure 1. Dissolve the active ingredient in the buffer solution. 2. Aseptically filter the solution from step 1. 3. The sterile solution is now aseptically filled into sterile ampoules 4. The ampoules are sealed under aseptic condition. Suppositories : Ingredients Per Supp. 1. Active ingredient 10.0 mg. 2. Polyethylene Glycol 1000 1350.0 mg. 3. Polyethylene Glycol 4000 450.0 mg. Procedure: 1. Melt 2 and 3 together and stir until uniform. 2. Dissolve No. 1 in the molten mass from step 1 and stir until uniform. 3. Pour the molten mass from step 2 into suppository moulds and chill. 4. remove the suppositoires from moulds and wrap. Therapeutic compositions for combatting histamine in unit dosage form, comprising a pharmaceutical carrier and an effective amount of a compound of Formula I or a pharmaceutically acceptable acid addition salt thereof are therefore an embodiment of this invention. Various modificAtions and equivalents will be apparent to one skilled in the art and may be made in the compounds, methods, processes and pharmaceutical compos it' ions of th'e present invent'ion without departing from the spirit and scope thereof, and it is therefore to be understood that the invention is to be limited only by the scope of the appended claims.

Claims: CLAIMS 1. A compound having the formula: EMI118.1 wherein: A represents an aromatic ring system having two of its carbon, atoms held-mutually with the cxazepine or thiazepine moiety selected from benzene . naphthalene, and pyridine in any of its four positions, any of the rings being optionally substituted by one or two Y -radicals selected from halo, loweralkyl, loweralkoxy, nitro and tri'fluoromethyl; 3 and'E are selected-'from oxygen and-sulphur and may be-the same or different; R is selected from hydrogen, lower-alkyl, cyclo alkyl or phenyl-loweralkyl of which phenyl is optionally substituted by one or two radicals selected from halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl; n n is 1,2 or 3; Z is selected from -NRÚRê ; 1H-pyrazol-1-yl and lH-imidazol-l-yl; each of RÚ and Rê is selected from hydrogen, loweralkyl, cycloalkyl and phenyl-loweralkyl of which phenyl is optionally substituted by 1 to 2 radicals selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl and cyano, or R1 and R2 taken together with the adjacent nitrogen atom form a heterocyclic residue selected from 1-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl, 1-piperidinyl, 4-substituted piperidine-l-yl, 4-morpholinyl, 1 piperazinyl, 4-substituted piperazin-l-yl and 1,2,3,6-tetrahydropyridin-1-yl and the pharmaceutically acceptable salts thereof with the proviso that when R=H, Z is never a primary or secondary amine and a further proviso that when n=3, Z is not lH-pyrazol-lyl, lH-imidazol-l-yl, 2,5-dimethylpyrrolidin-l-yl, 2-methylpyrrolidin-l-yl or 1,2,3,6-tetrahydropyridin1-yl. 2. A compound as claimed in Claim 1, wherein n is 2. 3. A compound as claimed in Claim 1 or 2, wherein A represents a benzene ring. 4. A compound as claimed in Claim 1 or 2, wherein A represents a naphthalene ring system. 5. A compound as claimed in-Ciaim 1 or 2, where- in A represents a pyridine ring. 6. A compound as claimed in any one of Claims 1 to 5, wherein the ring'represented by A is substituted by one or more chlorine or bromine atoms or by a methoxy group. 7, A compound as claimed in any one of Claims 1 to 6.wherein R represents a methyl, ethyl, benzyl or hexyl group. 8. A compound as claimed in any one of Claims 1 to 7, wherein Z represents a dimethylamino group. g. 2-[2-(Dimethylamino)ethyl]-2,3-dihydro-4methyl-1,4-benzoxazepin-5(4H)-one, 2,3-dihydro4-methyl-2-[2-(4-morpholino)ethyl]-1,4-benzoxazepin5(4H)one, 4-benzyl-2,3-dihydro-2-[2-(4-morpholino) ethyl]-1,4-benzoxazepin-5(4H) one, 4-benzyl-2,3dihydro-2-[2-(methylamino)ethyl]-1,4-benzoaxazepin-5(4H)one, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methyl-1, 4-benzoaxazepine-5(4H)-thione, 4-benzyl-2-[2-(dimethylamino)ethyl]-2,3-dihydro-1,4-benzoxazepin-5(4H)one, 2,3-dihydro-4-methyl-2-[2-(4-morpholino)ethyl]-1, 4-benzoxazepine-5(4H)-thione, 2-[2-(dimethylamino)ethyl] -2,3-dihydro-4-methylnaphth[2,3-f][1,4]oxazepin-5(4H)one, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methylpyrido[3,2-f][1,4] oxazepin-5(4H)-one, 2-[2 (dimethylamine) ethyl]-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]oxazepine-5(4H)-thione, 4-benzyl-2,3-dihydro-2-[2 (4-morpholino)ethyl]-1,4-benzoxazepine-5(4H)-thione, 2,3-dihydro-4-methyl-2-[2-(methylamino)ethyl]-1,4benzoxazepin-5(4H)-one, 2,3-dihydro-4-methyl-2-[2-(methylamino)ethyl]-1,4-benzoxazepin-5(4H)-one fumarate, 2,3-dihydro-2-[2-(4-hydroxy-4-phenyl)-piperidinylethyl]4-methyl-1,4-benzoxazepine-5(4H)-thione, 2,3-dihydro4-methyl-2- 2-(4-phenyl-1,2,3,6-tetrahydro)pyridinyl ethyl -1,4-benzoxazepine-5(4H)-thione, 8-chloro-2 [2-(dimethylamino)ethyl]-2,3-dihydro-4-methyl-1,4benzoxazepine-5(4H)-thione, 8-chloro-2-[2-(dimethylamino) ethyl]-2,3-dihydro-4-methyl-1,4-benzoxazepin-5(4H)one, 7-bromo-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4methyl-1, 4-benzoxazepin-5(4H)-thione, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methylnaphth. [2,1-f][1,4]oxazepin-5(4H)-one, 2-[2-(dimethylamino) ethyl]-2,3-dihydro-4-methylpyrido[4,3-f][1,4] oxazepine-5(4H)-thione, 2-[2-(dimethylamino)ethyl]-2, 3-dihydro-4-methylnaphth[2,3-f][1,4]-oxazepine-5(4H) thione, 7-chloro-2-[2-(dimethylamino)ethyl]-2, 3 dihydro-4-methyl-1,4-benzoxazepin-5-(4H)-one, 2 [2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepine-5(4H)-thione methiodide, 7-chloro-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4 methyl-1,4- benzoxazepine-5 (4H)-thione, 2-[2-(dimethyl amino)ethyl]-2,3-dihydro-4-methylnaphth]2,1-f][1,4] oxazepine-5(4H)-thione, 2- 2-(dimethylamino)ethyl -2, 3-dihydro-7-methoxy-4-methyl-1,4-benzoxapin-5(4H)-one, 7-bromo-2-[2-(dimethylamino)ethyl]-2,3-dihydro-4-methyl 1,4-benzoxazepine -5(4H)-thione, 2-[2-dimethyl-amino) ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]-thiazepin 5(4H)-one, 2-[2-(dimethylamino)ethyl]-2,3-dihydro-4 methylpyrido[3,2-f][1,4]-thiazepine-5 (4H)-thione, 2 [2-(dimethylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,4-f][1,4]-oxazepin-5(4H)-one, 2-[2-(dimethylamino) ethyl]-2,3-dihydro-4-methylpyrido[3,4-f]oxazepin-5(4H) thione, 2-(3-aminopropyl)-2,3-dihydro-4-methyl-pyrido [3,2-f][1,4]-oxazapin-5(4H)-one, 2,3-dihydro-4-methyl 2-[2-(4-morpholinyl)ethyl]-pyrido[3,2-f][1,4] oxazepin-5(4H)-one, 2,3-dihydro-4-methyl-2-[2-(1 pyrrolidinyl)ethyl]-pyrido[3,2-f][1,4]-oxazepin-5 (4H)-one, 2-[2-(dibutylamino)ethyl]-2,3-dihydro-4 methyl-pyrido[3,2-f][1,4]-oxazepin-5(4H)-one, 2-[2 (diethylamino)ethyl]-2,3-dihydro-4-methylpyrido-[3,2 f][1,4]-oxaxepin-5(4H) one, 2,3-dihydro-4-methyl2-[2-(1-piperidinyl)ethylpyrido[3,2-f][1,4]-oxazepin5(4H)-one, 2,3-dihydro-4-methyl-2-[2-(methyl(phenylmethyl)amino)ethyl]pyrido-[3,2-f][1,4]-oxazepin-5(4H)one, 2,3-dihydro-4-methyl-2-[2-(methylphenylamino) ethyl]pyrido [3,2-f][1,4]-oxazepin-5-(4H)-one, 2-[2-(2,5-dimethyl-1-pyrrolidinyl)ethyl-2,3-dihydro4-methyl-pyrido[3,2-f][1,4]-oxazepin-5(4H)-one, 2,3dihydro-4-methyl-2-[2-(2-methyl-1-pyrrolidinyl)ethyl] pyrido-[3,2-f][1,4]-oxazepin-5(4H)-one, 2,3-dihydro4-methyl-2-[2-(1H-pyrazol-1-yl)ethyl]-pyrido[3,2-f][1,4]oxazepin-5-(4H)-one, 2,3-dihydro-2-[2-(1H-imidazol-1yl)ethyl -4-methylpyrido[3,2-f] [1,4] oxazepin-5(4H)one, 2-[2-(dimethylamino)ethyl]-4-ethyl-2,3-dihydropyrido[3,2-f][1,4]-oxazepin-5(4H)-one, 2,3-dihydro4-ethyl-2-[2-(1-pyrrolidinyl)ethyl]pyrido[3,2-f] [1,4] oxazepin-5(4H)-one, 2,3-dihydro-4-methyl-2-[2-(4-morpholinyl)ethyl] pyrido[3,2-f][1,4]oxazepin-5(4H)-[hione, 2-[2-(dibutylamino)ethyl]-2,3-dihydro-4-methylpyrido [3,2-f][1,4]-oxazepin-5(4H)-thione, 2-[2-(diethylamino) ethyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5-(4H)-thione, 2,3-dihydro-4-methyl-2-2[ (1-pyrrolidinyl)ethyl]pyrido-[3,2-f][1,4]oxazepine5(4H)-thione, 2,3-dihydro-2-[2-(1H-imidazol-1-yl) ethyl]-4-methylpyrido[3,2-f][1,4]-oxaepine-5(4H) thione, 2-[2-(dimethyl-amino)ethyl]-4-ethyl-2,3 dihydropyrido±3, 2f Ll, 4.3-oxazepin-5 (4H) -thione, 2,3-dihydro-4-methyl-2-[2-[methyl(phenylmethyl)amino] ethyl]pyrido[3,2-f][1,4]-oxazepine-5(4H)-thione, 2,3-dihydro-2-[methylamino)ethyl]-4-methylpyrido [3,2-f][1,4]-oxazepine-5(4H)-thione, 7-chloro-2,3dihydro-4-methyl-2-[2-(1-pyrrolidino)ethyl]pyrido [3,2-f][1,4]-oxazepin-5 (4H)-one- 7-chloro-2[2-(dimethyl amino) ethyl @ 2 ,3-dihydro- 4-methylpyrido 3,2-f oxazepin-5 (4H) -one, 2- [2- (dimethylamino ethyl-2,3- dihydro-4-phenylmethylpyrido[3,2-f][1,4]-oxazepin-5 (4H)-one, 2-[2-(dimethylamino)ethyl-2,3-dihydropyrido [3,2-f][1,4 -oxazepin-5(4H)-one, 2-[3-(dimethylamino) propyl]-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepin-5 (4H)-one, 2-[3-(dimethylamino)propyl]-2,3dihydro-4-methylpyrido[3,2-f][1,4]- oxazepine-5(4H)thione or 7-chloro-2-[2-(dimethylamino)ethyl] 2,3dihydro-4-methylpyrido-[3,2-f]oxazepine-5(4H)-thione or, where appropriate, a pharmaceutically acceptable salt thereof. 10. A compound having the formula: EMI123.1 wherein: A represents an aromatic ring system having two of its carbon atoms held mutually with the oxazepine or thiazepine moiety selected from benzene, naphthalene, and.pyridine in any of its four positions, any of the rings being optionally substituted by one or two Y radicals selected from halo,loweralkyl,loweralkoxy, nitro and trifluoromethyl; B and E are selected from oxygen and sulphur and may be the same or different; R is selected from hydrogen, lower alkyl, cycloalkyl or phenyl-loweralkyl of which phenyl is optionally substituted by one or two radicals selected from halo;loweralkyl, loweralkoxy, nitro and trifluoromethyl; n is 1,2 or 3;. Z is selected from -NRÚRê ; 1H-pyrazol-1-yl and 1H imidazol-l-yl; each of R1 -and R2 is selected from hydrogen, loweralkyl, cycloalkyl and phenyl-loweralkyl of which phenyl is optionally substituted. by 1 or 2 radicals selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl and cyano, or'R1 and R2 taken together. with the adjacent nitrogen atom form a heterocyclic residue selected from 1-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl, 1-piperidinyl, 4-substituted piperidine-1-yl, 4-morpholinyl, 1-piperazinyl, 4-substituted plperazin-1-yl and 1.2, 3,6-tetrahydro-pyridin-1-yl and the pharmaceutically acceptable salts thereof with the proviso that when -R=H, Z is never a primary or -secondary -amine and' a further proviso that when n=3, Z is not 1H-pyrazol-1 yl, 1H-imidazol-1-yl, 2, 5-dimethylpyrrolidin-1-yl, 2 methylpyrrolidin-1-yl for use in medicine. 11. A compound as-claimed in any one of Claims 2 to 9 for use in medicine. 12. A process for the preparation of a compound or. .thiazepine of the formula EMI124.1 wherein A represents an aromatic ring system having two of its carbon atoms.held mutually with the oxazepine or thiazepine moiety selected from benzene, naphthalene or a pyridine.in any of its four positions, any of the rings being-optionally substituted by one or two Y radicals selected from halo, loweralkyl, loweralkoxy, nitro ana. trifluoromethyl; B & E are selected from.oxygen and sulphur and may be the same or different; R is seleected from hydrogen, loweralkyl, cycloalkyl, or phenyl-loweralkyl of which phenyl is optionally substituted-.by one or two radicals selected from halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl; n is 1, 2 or 3; ; Z is selected from -NRÚRê, 1-H-pyrazol-1-yl or 1H-imidazol-1-yl ; RÚ and Rê are selected from hydrogen, loweralkyl, cycloalkyl. and phenyl-loweralkyl of which phenyl is optionally substituted by.l-or radicals - selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl and cyano, or RÚ and Rê taken together with the adjacent nitrogen atom -form-a heterocyclic residue selected from l-pyrrolidinyl, 2,5-dimethylpyrrolidin-l-yl, 2Lmethylpyrrolidin-l-yl, l-piperidinyl, 4-substituted piperidine-l-yl, 4-morpholinyl, l-piperazinyl, 4substituted piperazin-1-yl and 1,2,3,6-tetrahydropyridinl-yl and 'the. pharmaceutically acceptable salts thereof with the proviso that when -R is hydrogen Z is never a primary or secondary amine and a further proviso that when.n=3, Z is not 1H-pyrazol-1-yl, lH- imidazol-l-yl, 2 , 5-dimethylpyrrolidin- l-yl , 2-methylpyrrolidin-1-yl or 1,2,3,6-tetrahydropyridin-1-yl, the process comprising either i) reacting a compound of the formula EMI126.1 wherein A,B,E,R,Y and n are as defined for formula I and X represents chlorine, bromine or cyano with a compound of the formula ZH wherein Z is as defined for formula I ; or ii) reducing-a compound of the formula EMI126.2 to give a compound.of formula I in which represents oxygen, Z represents.-NH2 and n is 2 or 3, and if necessary iii) -convertinga'-compound of formula I so formed into another-compound of-formula I; and optionally iv) preparing a. pharmaceutically acceptable salt of a compound so formed. 13. A process as claimed in Claim 12 for preparing a compound as claimed in any one of Claims 2 to 9. 14. A compound of the formula: EMI127.1 wherein: A represents an aromatic ring system having two of its carbon atoms held.mutually with the oxazepine or thiazepine moiety selected from benzene, a naphthalene and a pyridine in any of its four positions, any of which ring systems are optionally substituted by one or two Y radicals selected from halo, loweralkyl, loweralkoxy, nitro or trifluoromethyl; B and are selected from oxygen and sulphur"" and may be the same or different ; R is selected from loweralkyl, cycloalkyl or phenylloweralkyl wherein phenyl is optionally substituted by 'one- 'or--two radicals selected from halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl; n is 1 or 2; ; X is chlorine, bromine or cyano; and the acid addition salts thereof. 15. A compound as claimed in Claim 14, wherein n is z. 16; A compound as claimed in Claim 14 or wherein A represents a benzene ring. 17. A compound as claimed in Claim 15 or 15, wherein A repesents a naphthalene ring system. 18. A compound as claimed in Claim 13 or 14, wherein A represents a pyridine ring. 19 A compound as claimed in any one of claims 13 to 17, wherein the ring represented by A is substituted by one or more chlorine or bromine atoms or by a methoxy group. 20.A compound as claimed in any one of Claims 13 to 18, wherein R represents a methyl, ethyl, benzyl or hexyl group. 21.2-(2-Chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepin-5-(4H)-one, 4-benzyl-2-(2-chloroethyl) 2,3-dihydro-1-,4-benzox2zepin-5çlH3-one,-2-(2-chlorÏ- ethyl)-2,3-dihydro-4-methylnaphth-[2,3-f] [1,4] oxa zepin-5(4S > -one, 2-(2-chloroethyl)-2,3-dihydro-4- methylpyrido[3,2-f] [1,4]-oxazepin-5(4H)-one, 8-chloro2-(2-chloroethyl)-2,3-dihydro-4-methyl 1-,4-benzoxapin5(4H)-one, 7-bromo-2-(2-chloroethyl)-2,3-dihydro-4methyl-1,4-benzoxazepin-5(4H)-one,7-chloro-2-(2-chloro ethyl)-2,3-dihydro--4-methyl-1,4-benzoxazepin-5(4H)- one, 2-(2-chloroethyl)-2,3-dihydro-4-methylnaphth [2,1-f][1,4]-oxazepin-5(4H)-one, 2-(2-chloroethyl)2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5(4H)one, 2-(2-chloroethyl)-2,3-dihydro-4-methyl-1, 4-benzoaxzepine5(4H)-thione. 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido [3,2-f] [1,4]-oxazepin-5(4H)-thione, 2-(2-chloroethyl)2,3-dihydro-4-methylnaphth[2,3-f] [1,4]oxazepine-5 (4H)-thione, 8-chloro-2-(2-chloroethyl)-2,3-dihydro 4-methyl-1,4-benzoxazepine-5(4H)-thione,7-bromo-2 (2-chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine5(4H)-thione, 2-(2-chloroethyl)-2,3-dihydro-4-methylnapth [2,1-f] [1,4] oxazepine-5(4H)-thione, 2(2-chloroethyl)-2,3-dihydro -4-methyl-pyrido[4,3-f][1,4]oxazepine-5(4H)-one, 7-chloro-2 (2chloroethyl)-2,3-dihydro-4-methyl-1,4-benzoxazepine-5(4H)-thione, 2-(2-chloroethyl)-2,3-dihydro-4-methyl-pyrido[4,3-f][1,4] oxazepine5(4H)-thione, 2-(2-chloroethyl-2,3-dihydro-7-methoxy-4-methyl-1,4benzoxazepine-5(4H)-thione, 2-(2-chloroethyl)-2,3-dihydro-4methylpyrido[3,2-f][1,4]-thiazepin-5(4H)-one, 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f] [1,4]-thiazepine-5(4H)-thione, 2-(2-chloroethyl)-2, 3-dihydro-4-methylpyrido[3,4-f] [1,4] [1,4]oxazepin-5(4H)one, 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido [3,4-f] [1-4] oxazepine-5(4H)-thione, 2,3,4,5-tetrahydro-4-methyl-5-oxopyrido[3,2-f] [1,4] oxazepine-2propanenitrile, 2- [2-chloroethyl) -4-ethyl-2, 3 dihydropyrido [3,2- Ll,40-oxazepin-S-(4H)-one, 2 (2-chloroethyl)-4-ethyl-2,3-dihydropyrido[3,2-f] [1,4] oxazepin-5(4H)-thione, 7-chloro-2-(2-chloroethyl)2,3-dihydro-4-methylpyrido [3,2-f] [1,4]oxazepin-5-(4H)one, 7-chloro-2-(2-chloroethyl)-2, 3-dihydro-4-methylpyrido[3,2-f][1-4]oxazepine-5(4H)-thione or 2-(chloromethyl)-4-cyclohexyl-2,3-dihydropyrido[3,2-f] [1-4]oxazepin-5(4H)-one or an acid.addition salt thereof. 21.A process for the preparation of a compound of the formula : EMI130.1 wherein: A selected from an aromatic ring system having two of its carbon atoms held mutually with the oxazepine or thiazepine moiety selected from benzene, a naphthylene, a pyridine in any omits four positions, any of which ring system is optionally substituted by one or two Y radicals selected from halo, loweralkyl, loweralkoxy, nitro or trifluoromethyl; ^ B and E are selected from oxygen and sulphur and may be the same or different ; R.is selected from. loweralkyl, cycloalkyl or phenylloweralkyl wherein phenyl is optionally substituted by loweralkoxy, nitro or trifluoromethyl : : n is 1 or 2; X is chlorine, bromide or cyano or an acid addition salt thereof, the process comprising i) al . fusing a compound having the formula EMI132.1 - wherein x represents chlorine or bromine and A,E,n,R and Y are as defined above ; b) and when required reacting the compound so formed with a sulphurizing agent to obtain an oxazepinethione or a thiazepinethione ; and step optionally reacting a compound obtained.in step i)a) or i)b) with an alkali metal cyanide to obtain the corresponding compound in which X represents CN ; or ii) halogenating a compound obtained in step i)a), i)b) or i)c) having the formula EMI132.2 wherein E and R are as defined above and X is chlorine, bromine or cyano with sulphur chloride in a suitable solvent to obtain. a compound having the formula EMI132.3 wherein E and R are as defined above and X is chlorine, bromine or cyano. 23. A process as claimed in Claim 22 for preparing a compound as claimed in any one of Claims 15 to 21. 24. A compound selected from the group having the formula: EMI133.1 wherein: A represents an aromatic ring'system selected from benzene, a naphthalene or a pyridine in any of its four positions, any of which rings systemsis optionally substituted by one or two Y;radicals -- selected from halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl; R is selected from loweralkyl, cycloalkyl or phenylloweralkoxy, nitro and trifluoromethyl; n is 1 'or' 2, X is selected from chlorine, bromine and fluorine and E.is selected from sulphur and oxygen. 25. A compound having the formula: EMI133.2 wherein: A represents an aromatic ring system selected from a naphthalene or a pyridine in any of its four positions, any of which ring systems is optionally substituted by one or. two radicals selected from the group consisting of halo, loweralkyl, loweralkoxy nitro or- trifluoromethyl; R is selected from loweralkyl, cycloalkyl, and phenyl-loweralkyl wherein phenyl is optionally substituted by one or two radicals selected from halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl; n is 1 or 2; Q is selected from EMI134.1 cyano, EMI134.2 wherein R is H, an acid neutralizing ion for an esterifying radical, and E is oxygen or sulphur. 24. 3-[(1-Methyl-3-pyrrolidinyl)oxy]-2naphthalenecarboxamide, 3-[(1-methyl-3-pyrrolidinyl) oxy]-2-naphthalenecarboxylic acid, its oxalate salt, sodium 2-[(1-methyl-3-pyrrolidinyl)oxy]-3-pyridinecarboxylate, the free base thereof, l-f(l-methyl-3- pyrrolidinyl)oxy]-2-naphthalenecarboxamide, 3-[(1-methyl-3-pyrrolidinyl)oxy]-4-pyridinecarbonitrile, its fumarate salt, or 1-[(1-methyl-3-pyrrolidinyl), oxy}-2-napEthalenecarbonitrile or its oxalate salt 25. A pharmaceutically composition comprising a) a compound having the formula: EMI135.1 wherein: A represents an aromatic system, having two of its carbon atoms held mutually with the oxazepine or thiazepine moiety, selected from benzene, a naphthalene or a pyridine in any of its four positions, any of which ring systems--is optionally substituted by one or two Y radicals selected from ha:1, lowerÅalkyl, lower- alkoxy, nitro and trifluoromethyl ; B-and E are selected from oxygen and sulphur and may be the same.or different; R is selected from hydrogen, loweralkyl, cycloalkyl or phenylloweralkyl or Which phenyl may be optionally. substituted by one o two radicals selected from halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl and cyano; n is one, two or three; Z is selected from -NRÚRê, 1H-pyrazol-1-yl, or lH-imidazol-l-yl; each of R1 and R2 is selected from hydrogen, loweralkyl, cycloalkyl and phenylloweralkyl of which phenyl is optionally substituted by one or two radicals selected from. halo, loweralkyl, loweralkoxy, nitro, trifluoromethyl and cyano, or RÚ and Rê taken together with the adjacent nitrogen atom form a heterocyclic residue selected from 1-pyrrolidinyl, 2,5-dimethylpyrrolidin1-yl, 2-methyl-pyrrolidin-1-yl, 1-piperidinyl, 4-substituted piperidine-1-yl, 4-morpholinyl, 1-piperazinyl, 4-substituted piperazin-1-yl and 1,2,3,6-tetrahydropyridin-1-yl and the pharmaceutically acceptable salts thereof, with the proviso that when R=1I, Z is never a primary or secondary amine and a further proviso that when n=3, Z is not 1H-pyrazol-1-yl, 1H-imidazol1-yl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin1-yl or 1,2,3,6-tetrahydropyridin-1-yl, and b) a pharmaceutical carrier therefor. 28. A pharmaceutical composition comprising a) a compound as claimed in any one of Claims 2 to 11; and b) a pharmaceutical carrier therefor.

Inventors: CALE, ALBERT DUNCAN, JR., FRANKO, BERNARD VINCENT, LEONARD, CHARLES ARTHUR
Applicants: A.H. ROBINS COMPANY, INCORPORATED
Application year: 1983
Main classification: C07D267
IPC codes: C07D401, C07D413, C07D207, C07D513, C07D498, C07D267