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

HRID 1747149Notes

Reaction equation

HRID 1747149 reaction equation
[CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][C@@H:10]2[CH2:17][C@H:13]3[O:14][CH2:15][CH2:16][C@@:12]3([C:18]([N:20]3[CH2:29][CH2:28][C:27]4[N:26]=[CH:25][C:24]([C:30]([F:33])([F:32])[F:31])=[CH:23][C:22]=4[CH2:21]3)=[O:19])[CH2:11]2)[CH2:7][CH2:6][O:5][CH2:4]1.[C:34]([OH:41])(=[O:40])[CH2:35][CH2:36][C:37]([OH:39])=[O:38].C>CO>[C:34]([OH:41])(=[O:40])[CH2:35][CH2:36][C:37]([OH:39])=[O:38].[CH3:1][O:2][C@H:3]1[C@@H:8]([NH:9][C@@H:10]2[CH2:17][C@H:13]3[O:14][CH2:15][CH2:16][C@@:12]3([C:18]([N:20]3[CH2:29][CH2:28][C:27]4[N:26]=[CH:25][C:24]([C:30]([F:33])([F:31])[F:32])=[CH:23][C:22]=4[CH2:21]3)=[O:19])[CH2:11]2)[CH2:7][CH2:6][O:5][CH2:4]1

Participants

5

Reactant 3

HCID 297MethaneHCID 1110Succinic AcidHCID 60148505((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

Product 1

HCID 71745054((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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  1. dissolutionuntil dissolved
  2. dissolutionto dissolve
  3. filtrationThe mixture was filtered through Celite
  4. washwashed with MeOH
  5. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-a5b96877ac8448869342c1a2a0974017
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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