Process for the preparation of CCR-2 antagonists

US7361765B2 · kind B2 · utility

Assignee

• MERCK & CO., INC. · US

Inventors

• Dongwei Cai · Edison, US
• Fred J. Fleitz · Germantown, US
• Min Ge · Nanjing, CN
• Scott Hoerrner · Westfield, US
• Gary Javadi · Princeton, US
• Mark S. Jensen · Wake Forest, US
• Robert D. Larsen · Bound Brook, US
• Wenjie Li · Poughkeepsie, US
• Dorian Nelson · Windom, US
• Elizabeth Szumigala · Somerville, US
• Lihu Yang · Edison, US
• Changyou Zhou · Princeton, US

Key dates

• Filing date: Oct 25, 2004
• Grant date: Apr 22, 2008
• Expiry date: Dec 11, 2024

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2601/10
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention provides an efficient synthesis for the preparation of ((1R,3S)-3-isopropyl-3-{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-m ethoxytetrahydro-2H-pyran-4-yl]amine and its succinate salt. The present invention additionally provides an efficient syntheses for the preparation of intermediates (3R)-3-methoxytetrahydro-4H-pyran-4-one; (1S,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxylic acid; and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine; and for the preparation of the precursor (3S,4S)-N-((1S,4S)-4-isopropyl-4-{[3-(tri-fluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopent-2-en-1-yl)-3-methoxytetrahydro-2H-pyran-4-amine. The invention additionally resides in the superior properties of the succinate salt of ((1R,3S)-3-isopropyl-3-1{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine