Patent GB-1338235-A (GB)
Title: Azapurinones
IPC: C07D317/68
Filed: 1971-10-26
Abstract: 1338235 Azapurinones MAY & BAKER Ltd 14 Dec 1971 [15 Dec 1970 (2) 26 Oct 1971 17 Nov 1971] 59552/70 59556/70 49576/71 and 53457/71 Heading C2C [Also in Division A5] Novel compounds of Formula I, and their salts, in which R is a phenyl or naphthyl group optionally substituted by one or more of halo, OH, alkyl, phenylalkyl, alkoxy, alkenyloxy, alkynyloxy, alkoxyalkoxy, phenoxy, aralkoxy, alkylthio, hydroxyalkyl, NO 2 , alkanesulphonyl, alkanoyl, alkoxycarbonyl,NH 2 , CF 3 , -OCH 2 O- and amino groups substituted by one or two of alkyl, phenyl, alkanoyl, alkanesulphonyl and arenesulphonyl; or R is a 2-6 C alkenyl or alkynyl group, a 3-8 C cycloalkyl group, a 2-10 C alkyl group or a 1-10 C alkyl group substituted by one or more of halo, OH, 3-8 C cycloalkyl, 1-6 C alkoxy, and phenyl optionally substituted by one or more of halo, 1-6 C alkyl or alkoxy, OH and phenyl-1-6 C alkoxy; are prepared by (a) reacting compounds II with a nitrous acid source; (b) reacting compounds XIV  in which X<SP>n-</SP> is an anion of basicity n and R 3  and R 4  are H or 1-6 C alkyl, with compounds XV in which R 5  is OH, alkoxy, NH 2 , or mono- or dialkylamino; (c) reacting compounds XVIII R 6 CZ 3  in which R 6  is R in which C atom by which it is attached to the 2-position of the azapurine ring bears no H atom and Z is halo, with 5-amino- 4 - carbamoyl - 1H - 1,2,3 - triazole; (d) reacting compounds XV with compounds XII in which R 1  is 1-6 C alkyl and Y- is an anion; (e) reacting compounds XIX R 6 -(SR 1 ) 3  with 5 - amino - 4 - carbamoyl - 1H - 1,2,3 - triazole; (f) replacing the group R<SP>7</SP> of a compound XX in which R<SP>7</SP> is a nitrogen protecting group, e.g. benzyl, by H; (g) reacting 5-amino-4-carbamoyl-1H-1,2,3-triazole with compounds RCOZ; or (h) reacting compounds XXV with a source of nitrous acid; followed where desired by conventional modification of the R group by methods known per se. Compounds II may be prepared by reduction of compounds III or IV in which Ar is aryl. Compounds III may be prepared by reaction of compounds V with an alkyl α-oximinocyanoacetate or by nitrosation of compounds VI Compounds IV may be prepared by reaction of compounds V with compounds VII or by reaction of compounds VI with compounds VIII Compounds V may be prepared by reaction of acids HnX with compounds IX Compounds IX' may be prepared by catalytic hydrogenation of compounds X Compounds X may be prepared by reaction of NH 2 OH.HCl with compounds XI RCN. Compounds IX may also be prepared by reaction of compounds XII with alcoholic ammonia. Compounds XII may be prepared by reaction of HCl in R 1 OH with compounds XI or by reaction of the appropriate trialkyloxonium borofluoride or fluorosulphonate with compounds XIII RCONH 2 . Compounds VI may be prepared by reaction of compounds V with an alkyl cyanoacetate in the presence of an alkali metal alkoxide. Compounds XIV may be prepared by reaction of HnX with compounds XVI Compounds XVI may be prepared by reaction of amines XVII HNR 3 R 4  with compounds XII. Compounds XX may be prepared (1) by reaction of compounds XXI. with compounds XIV or (2), where R is R 6 , by reaction of compounds XXII. with compounds XIX or of compounds XXII with compounds XVIII or (3) by reaction of compounds XXIII RCOZ with compounds XXII or compounds XXIV or (4) by reaction of compounds XXI with compounds XII. Compounds XXV are prepared by reacting compounds XXVI with a nitrous acid source.  2-Isobutoxy-benzamide is prepared by reaction of salicylamide with isobutyl bromide. 2-Methane sulphonyl-benzamide is prepared by reacting the acid chloride with ammonia. Similarly prepared are 2-butanesulphonylbenzamide, 4 - benzyloxy - 2 - methoxybenzamide, 2,5- dibenzyloxybenzamide, 2 - (4 - methoxyphenoxy) benzamide, and 2,3-methylenedioxybenzamide. 2-Butanesulphonylbenzoic acid is prepared by reacting 2-butylmercaptobenzoic acid with H 2 O 2 . 5 - Benzyloxy - 2 - methoxybenzoic acid is prepared by reacting 5-benzyloxysalicylic acid with dimethyl sulphate. 2 - Methoxy - 5 - trifluoromethylbenzonitrile is prepared by reacting NaOCH 3  with 2-bromo-5- trifluoromethyl benzonitrile. 2 - Methoxy - 3,5 - dimethylbenzamide is prepared by reaction of the acid chloride with NH 3 . 2 - Methoxy - 3,5 - dimethylbenzoic acid is prepared by reacting the disodium salt of 2- hydroxy-3,5-dimethylbenzoic acid (prepared by reaction of the free hydroxy acid with Na in CH 3 OH) with dimethyl sulphate. 5 - t - Butyl - 2 - methoxybenzonitrile is prepared by reacting the 2-hydroxy compound with CH 3 I. 4 - Amino - 2 - isopropylpyrimid - 6 - one is prepared by reaction of isobutyramidine sulphate with ethyl cyanoacetate. 5 - Benzamido - 1 - benzyl - 4 - carbamoyl - 1,2,3- triazole is prepared by reaction of 1-benzyl-4- carbamoyl - 5 - formamido - 1,2,3 - triazole with benzoyl chloride; 5 - benzamido - 4 - benzoylcarbamoyl - 1 - benzyl - 1,2,3 - triazole is prepared from 5 - amino - 1 - benzyl - 4 - carbamoyl - 1,2,3- triazole by reaction with C 6 H 5 COCl; by reaction of 5 - amino - 1 - benzyl - 4 - carbamoyl - 1,2,3- triazole with C 6 H 5 COCl there is prepared a mixture of mono and di-benzoyl-derivatives; 5-amino- 1 - benzyl - 4 - methylcarbamoyl - 1,2,3 - triazole is prepared by reaction of ethyl cyanoacetate with CH 3 NH 2 /EtOH followed by reaction with benzyl azide. Other intermediates similarly prepared are 1 - benzyl - 5 - isovaleramido - 4 - isovalerylcarbamoyl - 1,2,3 - triazole; mono- and di - isovaleryl derivatives of 5-amino-1-benzyl-4-carbamoyl-1,2,3-triazole; and 5-benzamido-4-carbamoyl-Hl-1,2,3-triazole. 2-Decyloxy-benzamide is prepared from salicylamide and decyl bromide. 5 - Methyl - 2 - propoxy - benzamide is prepared from 5-methyl-salicylamide and propyl iodide. Triethyl 2 - methoxy - trithioorthobenzoate is prepared from 2-methoxybenzoyl chloride and ethylmercaptan.