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“Improved Process For The Preparation Of Vasopressin”

Abstract: The present invention relates to a process for the preparation of Vasopressin of formula (20) Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 (S-S bridge between Cysteines). The present invention further relates to a process for the purification of Vasopressin intermediate of formula (20).

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
13 August 2018
Publication Number
07/2020
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
radha@biophore.com
Parent Application

Applicants

Biophore India pharmaceuticals Pvt. Ltd
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Inventors

1. Manik Reddy Pullagurla
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
2. Jagadeesh Babu Rangisetty
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Specification

A process for the preparation of Vasopressin of formula (20)
comprising:
a) cyclization of formula (19)
to obtain formula (20A) using a suitable oxidizing agent;
b) purifying Vasopressin TFA salt of formula (20A) by Flash chromatography; and
c) isolating pure Vasopressin of formula (20)

2. The process as claimed in claim 1, wherein oxidizing agent used is selected from a group comprising hydrogen peroxide, dimethylsufoxide, iodine or the like, preferably dimethylsufoxide , more preferably a mixture of 4-10% DMSO in water.
3. The process as claimed in claim 1, wherein formula (19) is prepared by the process comprising:

a) loading first amino acid Fmoc-Gly-OH (1) on Rink Amide AM Resin (RAAM Resin) to obtain Fmoc-Gly-RAAM resin (2)
b) deprotecting Fmoc of intermediate of formula (4) and then coupling with the required amino acids using a suitable coupling agent in the said order, wherein the order of amino acids is Fmoc-Arg (Pbf)-OH, Fmoc-Pro-OH of formula (Fmoc-Cys(trt)-OH (7) Fmoc-Asn(trt)-OH (9) , Fmoc-Gln(trt)-OH (11), Fmoc-Phe-OH (13) , Fmoc-Tyr(tBu)-OH (15) , Fmoc-Cys(trt)-OH (17) in presence of coupling agent(s) and solvent(s) to give Fmoc-Cys(trt)-Tyr(tBu)-Phe-Gln(trt)-Asn(trt)-Cys(trt)-Pro-Arg(Pbf)-Gly-RAAMof intermediate (18); and
c) deprotecting Fmoc from intermediate of formula (18) and isolating formula (19)

4. The process as claimed in claim 3, wherein the deprotecting agent used to remove the Fmoc group is 20% piperidine in Dimethyl formamide (DMF).
5. The process as claimed in claim 3, wherein the coupling agent used is Oxyma along with N, N'-Diisopropylcarbodiimide (DIC).
6. The process as claimed in claim 3, wherein the cleaving agent used is Trifluoroacetic acid (TFA), Phenol, Triisopyl silane and water.
7. The process as claimed in claim 2, wherein the hydroxyl protecting group is selected from the group comprising of DMT (dimethoxy trityl), MMT (Methoxy trityl), TRT (Trityl), tert-butyl, t-butoxy carbonyl.

8. A process for the purification of Vasopressin (20), which comprises of:
i. providing a solution of Vasopressin trifiuoroacetate salt of formula
(20A) in a suitable diluent; ii. eluting the solution through flash chromatography; and . iii. isolating pure Vasopressin (20).
9. The process as claimed in claim 6, wherein the buffer used is selected from
trifluoroacetic acid (TFA), o-phosphoric acid (OPA), ammonium acetate or
mixtures thereof.

Documents

Application Documents

# Name Date
1 201841030341-PROVISIONAL SPECIFICATION [13-08-2018(online)].pdf 2018-08-13
2 201841030341-FORM 1 [13-08-2018(online)].pdf 2018-08-13
3 Form1_Proof of Right_27-08-2018.pdf 2018-08-27
4 Correspondence by Applicant_Form1_27-08-2018.pdf 2018-08-27
5 201841030341-FORM 3 [08-08-2019(online)].pdf 2019-08-08
6 201841030341-ENDORSEMENT BY INVENTORS [08-08-2019(online)].pdf 2019-08-08
7 201841030341-COMPLETE SPECIFICATION [08-08-2019(online)].pdf 2019-08-08
8 Correspondence by Agent _Submission Of Document_16-08-2019.pdf 2019-08-16