Back to results
US 9,309,220 B2Granted
Processes for the preparation of (S)-3-(4- (4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione and pharmaceutically acceptable forms thereof
AssigneeCelgene Corporation
InventorsJohn F. Traverse, Chengmin Zhang, Gregg B. Feigelson, Benjamin M. Cohen, William W. Leong
Life of this patent
Estimating the term…
Abstract
Provided are processes for the preparation of enantiomerically enriched or enantiomerically pure 3-(4-((4-(morpholinomethyl)benzyl)oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione, or a pharmaceutically acceptable form thereof.
Claims34
A process for preparing an enantiomerically enriched or enantiomerically pure compound of Formula (I):
- or a pharmaceutically acceptable form thereof, comprising
- (step_1.1) transforming an enantiomerically enriched or enantiomerically pure compound of Formula (II):
- or a salt thereof, wherein
- (i) Z1 is NHY, and Z2 is OR;
- or
- (ii) Z1 is OR, and Z2 is NHY;
- wherein
- R is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, or a suitable protecting group of a carboxy group;
- and
- Y is hydrogen, or a suitable amino protecting group;
- to an enantiomerically enriched or enantiomerically pure compound of Formula (III), or a salt thereof:
- wherein
- (i) Z3 is NHY, and Z4 is OH;
- or
- (ii) Z3 is OH, and Z4 is NHY;
- under conditions suitable for ester to acid transformation, wherein step 1.1 occurs in the presence of an acid;
- (step 1.2) cyclizing the enantiomerically enriched or enantiomerically pure compound of Formula (III) to an enantiomerically enriched or enantiomerically pure compound of Formula (I-a):
- under conditions suitable for cyclization;
- (step 1.3) where Y is an amino protecting group, deprotecting the enantiomerically enriched or enantiomerically pure compound of Formula (I-a) to an enantiomerically enriched or enantiomerically pure compound of Formula (I) under conditions suitable for deprotection;
- and
- (step 1.4) optionally transforming the enantiomerically enriched or enantiomerically pure compound of Formula (I) to a pharmaceutically acceptable salt thereof under conditions suitable for salt formation.
18 more elements
A process for preparing an enantiomerically enriched or enantiomerically pure compound of Formula (I):
- or a pharmaceutically acceptable form thereof, comprising
- (step_1.i) transforming an enantiomerically enriched or enantiomerically pure compound of Formula (II):
- or a salt thereof, wherein
- (i) Z1 is NHY, and Z2 is OR;
- or
- (ii) Z1 is OR, and Z2 is NHY;
- wherein
- R is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, or a suitable protecting group of a carboxy group;
- and
- Y is hydrogen, or a suitable amino protecting group;
- to an enantiomerically enriched or enantiomerically pure compound of Formula (I-a):
- under conditions suitable for cyclization, wherein step 1.i occurs in the presence of an acid;
- (step 1.3) where Y is an amino protecting group, deprotecting the enantiomerically enriched or enantiomerically pure compound of Formula (I-a) to an enantiomerically enriched or enantiomerically pure compound of Formula (I) under conditions suitable for deprotection;
- and
- (step 1.4) optionally transforming the enantiomerically enriched or enantiomerically pure compound of Formula (I) to a pharmaceutically acceptable salt thereof under conditions suitable for salt formation.
12 more elements
A process for preparing an enantiomerically enriched or enantiomerically pure compound of Formula (I):
- or a pharmaceutically acceptable form thereof, comprising
- (step_1.a) transforming an enantiomerically enriched or enantiomerically pure compound of Formula (II):
- or a salt thereof, wherein
- (i) Z1 is NHY, and Z2 is OR;
- or
- (ii) Z1 is OR, and Z2 is NHY;
- wherein
- R is substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, or a suitable protecting group of a carboxy group;
- and
- Y is a suitable amino protecting group;
- to an enantiomerically enriched or enantiomerically pure compound of Formula (I), or a salt thereof, under conditions suitable for cyclization and deprotection, wherein step 1.a occurs in the presence of an acid;
- and
- (step 1.4) optionally transforming the enantiomerically enriched or enantiomerically pure compound of Formula (I) to a pharmaceutically acceptable salt thereof under conditions suitable for salt formation.
10 more elements
Dependencies are inferred from the claim text.