Patent ID: 6784172
Filing Date: 2004-08-31
Classification: A61P,C07D

Abstract:
A process for the synthesis of compounds of formula I: whereinR is hydrogen; R1 and R2 are each, independently, selected from the group consisting of hydrogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, halogen, fluorinated alkyl of from 1 to 6 carbon atoms, â€”CN, â€”NHâ€”SO2-alkyl of 1-6 carbon atoms, â€”SO2â€”NHâ€”alkyl of 1-6 carbon atoms, alkyl amide of 1-6 carbon atoms, amino, alkylamino of 1-6 carbon atoms, dialkylamino of 1-6 carbon atoms per alkyl moiety, fluorinated alkoxy of 1-6 carbon atoms, acyl of 2-7 carbon atoms, and aroyl; R3 and R4 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, cycloalkyl of from 3 to 7 carbon atoms and â€”CH2-cycloalkyl of from 3 to 7 carbon atoms; wherein the dashed line indicates an optional double bond; the process comprising the steps of: a) acylating a benzodiazepine compound of the formula: to give an acylated benzodiazepine of the formula: wherein R1 represents alkyl of from 1 to 10 carbon atoms, or a benzyl or napthyl group; b) reacting the acylated benzodiazepine of step a) with a nitrosating agent to provide an acylated nitroso benzodiazepine compound of the formula: c) reducing the acylated nitroso benzodiazepine compound of step b) to yield an acylated 1-aminobenzodiazepine compound of the formula d) allowing the acylated 1-aminobenzodiazepine compound of step c) to react with a cyclopentanone compound of the formula: â€ƒto provide a cyclopentylideneamino benzodiazepine compound of the formula: e) reacting the cyclopentylideneamino benzodiazepine compound of step d) to provide an acylated compound of the formula: â€ƒand either f) deacylating the acylated compound of step e) to provide a compound of the formula: â€ƒwhich may optionally be reduced; or g) reducing the acylated compound of step e) to provide a reduced acylated compound of the formula: â€ƒand deacylating the reduced acylated compound of this step g) to provide a compound of the formula: