Patent GB-1447426-A (GB)
Title: Pyrrolo 3,4-d- pyrimidines and methods for their preparation
IPC: C07D207/34
Filed: 1974-03-20
Abstract: 1447426 Pyrrolo - [3,4 - d] - pyrimidine derivatives GRUPPO LEPETIT SpA 12 March 1975 [20 March 1974] 12387/74 Heading C2C Novel compounds of the Formula I wherein R when present is H or alkyl; R 1  is H, phenyl or phenyl substituted with methyl, ethyl, methoxy, hydroxy, fluoro, chloro or bromo; R 2  is hydrogen, alkyl, phenyl, carbo (C 1-3  alkoxy or carboxy ; R 7  is H, alkyl, benzyl or halo-substituted benzyl in which the substitution is on the benzene ring; D is a radical A, B or C whose carbon atoms are linked to the carbon atom of the pyrrole nucleus and wherein R 3  is alkyl or phenyl, and R 4  is H, alkyl or phenyl and one or other of the additional bonds "a" and "b" are present with the proviso that (1) when D is Formula A or B shown above "a" is the bond present and (2) when D is C "b" is the bond present and R is absent, where alkyl radicals unless otherwise specified are C 1-4 , and pharmaceutically acceptable acid addition salts thereof may be prepared by reacting a compound of the Formula II or an acid addition salt thereof wherein R 5  is C 1-3  alkoxy, C 1-4  alkyl or phenyl with a compound R 6 NCO wherein R 6  is hydrogen, alkali metal, C 1-4  alkyl or phenyl, optionally isolating the intermediate IV and cyclizing IV by treatment with a base, optionally followed, when R 2  is carbalkoxy, by hydrolysis to carboxy. 4 - Acetyl - 3 - amino - 5 - methyl - 2 - phenyl pyrrole and its hydrochloride is prepared by cyclization of 2-amino-2-phenyl acetonitrile with acetylacetone. Several other compounds of the Formula II in which R 7  and R are hydrogen are prepared by the same procedure. 4 - Benzoyl - 3 - ethylamino - 5 - methyl - 2- phenyl-pyrrole is prepared by acylating 3- amino - 4 - benzoyl - 5 - methyl - 2 - phenyl pyrrole hydrochloride to form the 3-(p-toluenesulphonamido)derivative and alkylating the amido group with diethylsulphate. The corresponding 3-isopropylamino compound is prepared by a similar method using isopropyl bromide. Treatment of the same 3-(p-toluenesulphonamido) derivative under more vigorous conditions with diethyl sulphate yields 4- benzoyl - 1 - ethyl - 3 - (N - ethyl - p - toluenesulphonaminido) - 5 - methyl - 2 - phenyl pyrrole which is hydrolysed to 4-benzoyl-1-ethyl-3- ethylamino - 5 - methyl - 2 - phenyl - pyrrole. 3 - Amino - 4 - benzoyl - 1 - ethyl - 5 - methyl- 2 - phenyl - pyrrole is prepared by reacting 3 - amino - 4 - benzoyl - 2 - phenyl - pyrrole hydrochloride with benzaldehyde to form the Schiff's base which with ethyl iodide in strong base yields 3-benzylideneamino-4-benzoyl-1-ethyl- 5 - methyl - 2 - phenyl - pyrrole which gives the required compound on hydrolysis. 4-Acetyl-3- amino - 1 - butyl - 5 - methyl - 2 - (p - tolyl) - pyrrole and 3 - amino - 1 - butyl - 4 - carbethoxy- 5 - methyl - 2 - phenyl - pyrrole hydrochloride are prepared by similar methods. 4 - Acetyl - 3 - (p - chlorobenzylamino) - 5- methyl - 2 - (o - tolyl) - pyrrole is prepared by reacting 4 - acetyl - 3 - amino - 5 - methyl- 2 - (o - tolyl) - pyrrole with p - chlorobenzaldehde and reducing the Schiff's base formed. Pharmaceutical compositions of compounds I or pharmaceutically acceptable salts thereof with the usual excipients show anti-inflammatory activity and are prostaglandin synthetase inhibitors when administered orally, rectally or parenterally. Some of the compounds also show CNS-depressant properties and are active on the hydric balance in warm blooded animals.