Methane → ((3aS,5S,6aR)-5-((3S,4S)-3-methoxytetrahydro-2H-pyran-4-ylamino)hexahydro-2H-cyclopenta[b]furan-3a-yl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone succinate

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Reaction Conditions

Reaction Steps

A solution of Example 30, Step L (608 g, 1.18 mol) in MeOH (6 L) was warmed to 40° C. until dissolved. Succinic acid (141.9 g, 1.20 mol) was added and the suspension was warmed to 50° C. which caused everything to dissolve. Darco G-60 charcoal (80 g) was added and the contents swirled for 20 min. The mixture was filtered through Celite, washed with MeOH, and the solvent was evaporated under reduced pressure to provide the title compound (i.e., the succinate salt) as an amorphous foam. The resulting foam was dissolved completely in MIBK (5 L, degassed) at reflux, the heating was stopped and the solution was allowed to cool. The solution was seeded at 104° C. with crystalline material, prepared as described in Example 52, and the solution was cooled to 38° C. over 4 h. The suspension was chilled to 4° C., filtered, washed with ice-cold 100 mL MIBK and the solid was allowed to dry under a positive nitrogen stream (protected from light) overnight. After some light milling, the product of Step M was collected as a white solid. 1H NMR (400 MHz, MeOD) δ=8.72 (s, 1H), 8.04-8.12 (m, 1H), 4.97 (d, J=4.4 Hz, 1H), 4.94 (s, 3H), 4.86 (s, 2H), 4.18-4.28 (m, 1H), 3.98 (d, J=11.7 Hz, 4H), 3.74-3.88 (m, 1H), 3.62-3.73 (m, 1H), 3.28-3.58 (m, 8H), 3.12-3.23 (m, 2H), 2.58-2.68 (m, 1H), 2.37-2.44 (m, 1H), 2.28-2.36 (m, 1H), 1.88 (m, 4H). Elemental Analysis calc for C27H36F3N3O8×0.2 H2O: C, 54.85; H, 6.21; F, 9.64; N, 7.11; KF 0.61. Found: C, 55.17; H, 6.07; F, 9.99; N, 7.11; KF, 0.64.

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