Patent ID: 6362331
Filing Date: 2002-03-26
Classification: C07D

Abstract:
A process for the preparation of a Pyrrolo[2,1-c][1,4]benzodiazepine of formula VI wherein R is H, OH, OAc and R1 is H, and n is 3 to 5, said process comprising reacting (2S)-N-[4-hydroxy-5-methoxy-2-nitrobenzyl]-pyrrolidine-2-carboxy-carbaldehyde diethyl thioacetal of formula I wherein R1 is H with a dibromoalkane in a aprotic water miscible organic solvent in the presence of mild inorganic base upto refluxing temperature for a period upto 48 hours, isolating (2S)-N-[4-(3-bromoalkoxy)-5-methoxy-2-nitrobenzoyl]pyrrolidine-2-carboxy carbaldehyde diethyl thioacetal of formula II wherein R1 is H, reacting the compound of formula II with a dilactam of formula III wherein R is H, OH or OAc in presence of a mild inorganic base in presence of an aprotic water miscible organic solvent upto refluxing temperature for a period upto 48 hours, isolating 8-{[(2S)-N-5-methoxy-2-nitrobenzoyl]pyrrolidin-2-carbaldehyde diethylthioacetal}-alkoxy-7-methoxy-2,3,5,10,11,11a-hydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione of formula IV wherein R is H, OH, or OAc and R1 is H and n is 3 to 5, reducing the above nitro compound of formula IV with SnCl22H2O in the presence of an organic solvent upto a reflux temperature, isolating the 8-[[(2S)-N-5-methoxy-2-aminobenzoyl]pyrrolidin-2-carbaldehyde diethylthioacetal]-alkoxy-7-methoxy-2,3,5,10,11,11a-hydro 1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-dione of formula V, wherein R is H, OH or OAc, R1 is H and n is 3 to 5, reacting the amino compound of formula V with a deprotecting agent to obtain the pyrrolo[2,1-c][1,4]benzodiazepines of formula VI wherein R, R1 and &mgr; are as stated above.