PROCESS FOR THE PREPARATION OF CCR-2 ANTAGONIST

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-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopent-2-e n-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-{[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl}cyclopentyl)[(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine. L'invention concerne une synthèse efficace pour l'élaboration de ((1R,3S)-3-isopropyle-3-{[3-(trifluorométhyle)-7,8-dihydro-1,6-naphthyridine-6(5H)-yle]carbonyle}cyclopentyle)[(3S,4S)-3-méthoxytétrahydro-2H-pyrane-4-yle]amine et son succinate correspondant, mais aussi une synthèse efficace pour l'élaboration d'intermédiaires (3R)-3-méthoxytétrahydro-4H-pyrane-4-one; (1S,4S)-4-(2,5-diméthyle-1H-pyrrole-1-yle)-1-isopropylcyclopent-2-ène-1-acide carboxylique; et 3-(trifluorométhyle)-5,6,7,8-tétrahydro-1,6-naphthyridine; ainsi que pour l'élaboration du précurseur (3S,4S)-N-((1S,4S)-4-isopropyle-4-{[3-(trifluorométhyle)-7,8-dihydro-1,6-naphthyridine-6(5H)-yle]carbonyle}cyclopent-2-èn-1-yle)-3-méthoxytétrahydro-2H-pyrane-4-amine. Enfin, l'invention concerne les propriétés supérieures du succinate de ((1R,3S)-3-isopropyle-3-{[3-(trifluorométhyle)-7,8-dihydro-1,6-naphthyridine-6(5H)-yle]carbonyle}cyclopentyle)[(3S,4S)-3-méthoxytétrahydro-2H-pyrane-4-yle]amine.