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US 6,784,172 B2Granted
Processes for preparation of cyclopenta[b][1,4]diazepino[6,7,1-hi]indoles and derivatives
AssigneeWyeth
InventorsAnnmarie Louise Sabb, Robert Lewis Vogel, Madelene Miyoko Antane, Panolil Raveendranath, Sreenivasulu Megati, Michael David Smith, James Albert Nelson
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Abstract
This invention provides processes for synthesizing compounds of formula I: wherein R is H or alkyl; R1, R2 are H, alkyl, alkoxy, halogen, fluorinated alkyl, —CN, alkyl sulfonamide, alkyl amide, amino, alkylamino, dialkylamino, fluorinated alkoxy, acyl, or aroyl; R3 and R4 are H, alkyl or cycloalkyl; the dashed line indicates an optional double bond; as well as intermediates and pharmaceutically acceptable salts thereof.
Claims10
A process for the synthesis of compounds of formula I:
- wherein
- R 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, —CN, —NH—SO2-alkyl of 1-6 carbon atoms, —SO2—NH—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 —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:
- to 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:
- and either
- f) deacylating the acylated compound of step e) to provide a compound of the formula:
- which may optionally be reduced;
- or
- g) reducing the acylated compound of step e) to provide a reduced acylated compound of the formula:
- and deacylating the reduced acylated compound of this step g) to provide a compound of the formula:
17 more elements
Dependencies are inferred from the claim text.