Back to results
US 8,481,782 B2Granted
Treprostinil production
AssigneeUnited Therapeutics Corporation
InventorsHitesh Batra, Raju Penmasta, Vijay Sharma, Sudersan M. Tuladhar, David A. Walsh
Life of this patent
Estimating the term…
Abstract
The present invention is directed to a novel method for preparing a synthetic intermediate for treprostinil via a stereoselective alkyne addition reaction. Also described are methods of preparing treprostinil comprising the alkyne addition reaction described herein as well as novel intermediates useful for synthesis prostacyclin derivatives, such as treprostinil.
Claims23
A method of preparing a compound represented by the following structural formula:
- or a pharmaceutically acceptable salt thereof, comprising:
- reacting a compound represented by structural formula (I):
- with a compound represented by structural formula (a):
- to form a compound represented by structural formula (A):
- wherein:
- P1 is an alcohol protecting group;
- R is —(CH2)mX;
- X is COOR1;
- R1 is an alkyl group;
- and
- m is 1, 2 or 3, wherein the process further comprises:
- (a) reacting the compound of structural formula (A) with a second alcohol protecting group to form a compound represented by structural formula (4):
- and
- (b) converting the compound of structural formula (4) to a tricyclic compound represented by structural formula (5):
- (c) hydrogenating the tricyclic compound of structural formula (5) to form a hydrogenated tricyclic compound represented by structural formula (6):
- and
- (d) converting the hydrogenated tricyclic compound represented by structural formula (6) to a compound represented by structural formula (IX):
- wherein said converting (d) accomplishes cleaving of the protective group P1 and ester hydrolysis of R1 in a single pot.
15 more elements
A method of preparing a compound represented by the following structural formula:
- or a pharmaceutically acceptable salt thereof, comprising:
- reacting a compound represented by structural formula (I):
- with a compound represented by structural formula (a):
- to form a compound represented by structural formula (A):
- wherein:
- P1 is an alcohol protecting group;
- R is —(CH2)mX;
- X is COOR1;
- R1 is a substituted or unsubstituted benzyl group;
- and
- m is 1, 2 or 3, wherein the process further comprises:
- (a) reacting the compound of structural formula (A) with a second alcohol protecting group to form a compound represented by structural formula (4):
- and
- (b) converting the compound of structural formula (4) to a tricyclic compound represented by structural formula (5):
- (c) hydrogenating the tricyclic compound of structural formula (5) to form a hydrogenated tricyclic compound represented by structural formula (6′):
- and
- (d) converting the hydrogenated tricyclic compound represented by structural formula (6′) to a compound represented by structural formula (IX):
14 more elements
Dependencies are inferred from the claim text.