Sodium triacetoxyborohydride → (3aR,5R,6aR)-Benzyl 5-((3-methoxytetrahydro-2H-pyran-4-yl)amino)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydrocyclopenta-[c]pyrrole-2(1H)-carboxylate

HRID 571353Notes

Reaction equation

HRID 571353 reaction equation
[NH2:1][C@@H:2]1[CH2:19][C@H:5]2[CH2:6][N:7]([C:9]([O:11][CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:10])[CH2:8][C@@:4]2([C:20]([N:22]2[CH2:31][CH2:30][C:29]3[N:28]=[CH:27][C:26]([C:32]([F:35])([F:34])[F:33])=[CH:25][C:24]=3[CH2:23]2)=[O:21])[CH2:3]1.[CH3:36][O:37][CH:38]1[C:43](=O)[CH2:42][CH2:41][O:40][CH2:39]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:36][O:37][CH:38]1[CH:43]([NH:1][C@@H:2]2[CH2:19][C@H:5]3[CH2:6][N:7]([C:9]([O:11][CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[O:10])[CH2:8][C@@:4]3([C:20]([N:22]3[CH2:31][CH2:30][C:29]4[N:28]=[CH:27][C:26]([C:32]([F:35])([F:34])[F:33])=[CH:25][C:24]=4[CH2:23]3)=[O:21])[CH2:3]2)[CH2:42][CH2:41][O:40][CH2:39]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 131732811(3aR,5R,6aR)-Benzyl 5-amino-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

Product 1

HCID 72946982(3aR,5R,6aR)-Benzyl 5-((3-methoxytetrahydro-2H-pyran-4-yl)amino)-3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydrocyclopenta-[c]pyrrole-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of the product from Step A (difluoroacetate, 97.45 mg, 0.136 mmol), 3-methoxydihydro-2H-pyran-4(3H)-one (35.4 mg, 0.272 mmol), 4 Å molecular sieves (60 mg) and TEA (0.19 mL, 1.36 mmol) in DCM (4 mL) was stirred at rt for 2 h, followed by addition of sodium triacetoxyborohydride (46.12 mg, 0.218 mmol). The resulting mixture was stirred at rt overnight. The reaction was quenched by addition of saturated NaHCO3 aqueous solution, extracted with DCM, dried over Na2SO4. After removal of solvent, the residue was purified by column chromatography (eluent: 5% 7N NH3 in MeOH in DCM) to give the product as a yellow foam. 1H-NMR (400 MHz, CDCl3): δ 1.56-2.12 (m, 7H), 2.31 (br. s., 1H), 2.55-2.67 (m, 1H), 3.06-3.21 (m, 3H), 3.24-4.16 (m, 14H), 4.71 (br. s., 2H), 5.12 (s, 2H), 7.29-7.44 (m, 5H), 7.69 (br. s., 1H), 8.72 (br. s., 1H); LC/MS: C31H37F3N4O5: m/z 603.0 (M+H).

Workup

  1. stirringThe resulting mixture was stirred at rt overnight
  2. customThe reaction was quenched by addition of saturated NaHCO3 aqueous solution
  3. extractionextracted with DCM
  4. dry with materialdried over Na2SO4
  5. customAfter removal of solvent
  6. customthe residue was purified by column chromatography (eluent: 5% 7N NH3 in MeOH in DCM)

Sources & evidence

ORD record
ord-4440fbc77ac54645afdcc1b06adce3df
Source dataset
uspto-grants-2015_05
Patent number
US09024017B2

Reaction notes

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