ChemicalBook CAS DataBase List lifitegrast

lifitegrast synthesis

5synthesis methods

Product Name:lifitegrast
CAS Number:1025967-78-5
Molecular formula:C29H24Cl2N2O7S
Molecular Weight:615.48

Lifitegrast, also known as SAR-1118, is an LFA-1 antagonist intended for the treatment of vascular complications of the eye. Lifitegrast inhibits T cell-mediated inflammation by blocking the binding of two important cell surface proteins (lymphocyte function-associated antigen 1 and intercellular adhesion molecule 1), thus lessening overall inflammatory responses. Synthetic Description Reference: Burnier, John; Gadek, Thomas; Naud, Frederic. Crystalline pharmaceutical LFA-1 inhibitors and methods of preparation and use thereof. WO 2009139817. (Assignee Sarcode Corporation, USA) Synthetic Description Reference: Burnier, John. Preparation of crystalline isoquinoline derivative as LFA-1 inhibitor. US 20110092707. (Assignee Sarcode Corporation, USA) Synthetic Description Reference: Zeller, James Robert; Venkatraman, Sripathy; Brot, Elisabeth C. A.; Iyer, Subashree; Hall, Michael. Method for preparation of N-benzofuranylcarbonyl-5,7-dichloro-1,2,3,4-tetrahydro-6-isoquinolinylcarbonyl-3-(methylsulfonyl)-L-phenylalanine as LFA-1 inhibitor and polymorph thereof. WO 2014018748. (Assignee Sarcode Bioscience Inc., USA) Synthetic Description Reference: Anon. S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4- tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl) propanoic acid. Volume 17. Issue 9A. Pages 1-2.( Journal; Patent) Synthetic Description Reference: Wu, Ming-Chih; Hsiao, Tsung-Yu. Process for preparing Lifitegrast and intermediates thereof. WO 2019004936. (Assignee Scinopharm Taiwan, Ltd., Taiwan; Scinopharm Singapore Pte, Ltd.) Synthetic Description Reference: Berzosa Rodriguez, Xavier; Marquillas Olondriz, Francisco. Process for preparing and purifying the LFA-1 antagonist Lifitegrast. WO 2019020580. (Assignee Interquim, S.A., Spain) Synthetic Description Reference: Rajan, Srinivasan Thirumalai; Eswaraiah, Sajja; Reddy, Ghojala Venkat; Reddy, Sagyam Rajeshwar; Srinivasulu, Rangineni; Rajashekar, Kommera. Processes for the preparation of (s)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl) propanoic acid and polymorphs thereof. WO 2019043724. (Assignee MSN Laboratories Private Limited, R&D Center, India)

Synthetic Routes

ROUTE 1

ROUTE 2

ROUTE 3

ROUTE 4

ROUTE 5

ROUTE 6

ROUTE 7

Reference: Burnier, John; Gadek, Thomas; Naud, Frederic. Crystalline pharmaceutical LFA-1 inhibitors and methods of preparation and use thereof. WO 2009139817. (Assignee Sarcode Corporation, USA)

1194550-67-8 Synthesis

benzyl (S)-2-(2-(benzofuran-6-carbonyl)-5,7-dichloro-1,2,3,4-tetrahydroisoquinoline-6-carboxamido)-3-(3-(methylsulfonyl)phenyl)propanoate

1194550-67-8
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1025967-78-5
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Yield: 98.5 % ee

Reaction Conditions:

with formic acid;palladium 10% on activated carbon;triethylamine in tetrahydrofuran;methanolReagent/catalyst;Solvent;

Steps:

5.2; 7
[00143] The benzyl ester of compound 19 was removed by transfer hydrogenolysis using10% palladium on carbon, using formic acid and triethylamine in a 5:1 mixture of methanol:THF, to produce the compound of Formula I in 95% yield.

References:

SARCODE BIOSCIENCE INC.;ZELLER, James, Robert;VENKATRAMAN, Sripathy;BROT, Elisabeth, C.A.;IYER, Subashree;HALL, Michael WO2014/18748, 2014, A1 Location in patent:Paragraph 00141; 00143; 00149; 00152; 00153

77095-51-3 Synthesis