Patent GB-1077272-A (GB)
Title: Novel thiaza heterocyclics and a process for the manufacture thereof
IPC: C07D279/04
Filed: 1966-03-31
Abstract: The invention comprises compounds of the formula <FORM:1077272/C2/1> wherein Z represents either an orthophenylene group, or a methylene group which may carry C1- 7 alkyl or C1- 7 carboxyalkyl and/or C1- 7 alkyl or C1- 7 alkanoyloxy substitution, or an ethylene group which may carry similar substitution at one of its carbon atoms, R1, R2 and R3 each represent a halogen atom or a C1- 7 alkyl or C1- 7 alkoxy group, R4 and R5 each represent a C1- 7 alkyl or benzyl group or jointly, together with the nitrogen atom to which they are attached, form a 5- or 6-membered heteromonocyclic ring which may contain one further nitrogen or oxygen atom and which may contain one substituent, R6 represents a C1- 7 alkyl group, R7 represents a C1- 7 alkyl, phenyl or halophenyl group, n represents 2,3,4,5,6 or 7 and the broken lines denote that the group or atoms attached thereby are optional; acid addition salts thereof; and their preparation by reacting a compound of the formula <FORM:1077272/C2/2> either with a compound of the formula <FORM:1077272/C2/3> or with a compound of the formula X-CnH2n-Hal in which formulae X represents a halogen atom or a sulphonyloxy group and X represents a chlorine, bromine or iodine atom, and treating the reaction product with an amine of the formula <FORM:1077272/C2/4> and in either case, converting any carbonyl group present into a methylene group if desired, oxidizing any thio group present to a sulphinyl or sulphonyl group if desired, introducing a C1- 7 alkanoyloxy group on the carbon atom adjacent to the thio atom if required and, also if desired, converting the product into an acid addition salt.  Starting materials of the Formula (II) are prepared by (a) reacting a compound of the formula <FORM:1077272/C2/5> with a mercapto acid of the formula <FORM:1077272/C2/6> in which Z1 represents either an orthophenylene group, or a methylene group which may carry a C1- 7 alkyl or C1- 7 carboxyalkyl group as one substituent and a C1- 7 alkyl group as an optional second substituent, or an ethylene group which may be similarly monosubstituted or disubstituted at one of its carbon atoms, to form a 2-nitrobenzylthio acid of the formula <FORM:1077272/C2/7> reducing this to the corresponding 2-amino-benzylthio acid and then cyclizing this amino compound, after oxidizing the thio group therein to the sulphonyl group if desired), converting the carbonyl group in the product to the methylene group if desired, oxidizing any thio group present to a sulphinyl or sulphonyl group if desired, and introducing a C1- 7 alkanoyloxy group on the carbon atom adjacent to the thio atom if required, or (b) reacting a 2-aminobenzylmercapto compound of the formula <FORM:1077272/C2/8> with a halo-acyl halide of the formula <FORM:1077272/C2/90> (to prepare compounds of the Formula (II) wherein the carbonyl group adjacent to the nitrogen atom is present, R6 is absent, Z represents a methylene group which may carry a C1- 7 alkyl group as a substituent and no S-oxide is present.) 2-Aminobenzylmercapto compounds of the formula IX are prepared by reacting a compound of the formula <FORM:1077272/C2/101> with carbon disulphide in the presence of a tertiary amine to produce a benzoxazine of the formula <FORM:1077272/C2/112> heating this compound to produce a benzthiazine of the formula <FORM:1077272/C2/123> which is then ring-opened by treatment with an aqueous-alkaline medium.  Benzthiazines of the Formula (XIII) are also prepared by heating a compound of the Formula (XI) with carbon disulphide and a base to form a benzthiazine of the formula <FORM:1077272/C2/134> which is then treated with an oxidizing agent. 2 - (N - Methyl - benzylamino) - ethyl chloride is prepared by reacting methylamine with benzaldehyde and hydrogen, followed by treatment with sodium borohydride and ethylene oxide to form 2-(N-methyl-benzylamino)-ethanol which is then reacted with thionyl chloride.  2 - Amino - 4 - chloro - benzhydrol is prepared by reducing 2-amino-4-chloro-benzophenone with sodium borohydride. Pharmaceutical compositions having anti-depressant activity, for enteral or parenteral administration, comprise a compound of the invention together with a pharmaceutical carrier.