Sodium triacetoxyborohydride → (3aR,5R,6aR)-5-(((3S*,4S*)-3-Methoxytetrahydro-2H-pyran-4-yl)amino)-3a-(7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)hexahydrocyclopenta-[c]pyrrole-2(1H)-carboxamide

HRID 571357Notes

Reaction equation

HRID 571357 reaction equation
[NH2:1][C@@H:2]1[CH2:12][C@H:5]2[CH2:6][N:7]([C:9]([NH2:11])=[O:10])[CH2:8][C@@:4]2([C:13]([N:15]2[CH2:24][CH2:23][C:22]3[C:17](=[CH:18][C:19]([C:25]([F:28])([F:27])[F:26])=[CH:20][CH:21]=3)[CH2:16]2)=[O:14])[CH2:3]1.[CH3:29][O:30][CH:31]1[C:36](=O)[CH2:35][CH2:34][O:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:29][O:30][C@H:31]1[C@@H:36]([NH:1][C@@H:2]2[CH2:12][C@H:5]3[CH2:6][N:7]([C:9]([NH2:11])=[O:10])[CH2:8][C@@:4]3([C:13]([N:15]3[CH2:24][CH2:23][C:22]4[C:17](=[CH:18][C:19]([C:25]([F:28])([F:27])[F:26])=[CH:20][CH:21]=4)[CH2:16]3)=[O:14])[CH2:3]2)[CH2:35][CH2:34][O:33][CH2:32]1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 235336103-Methoxyoxan-4-oneHCID 86708901(3aR,5R,6aR)-5-Amino-3a-(7-(trifluoromethyl)-1,2,3,4-tetrahydro-isoquinoline-2-carbonyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxamide

Product 1

HCID 86708904(3aR,5R,6aR)-5-(((3S*,4S*)-3-Methoxytetrahydro-2H-pyran-4-yl)amino)-3a-(7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)hexahydrocyclopenta-[c]pyrrole-2(1H)-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of the product from Step B (316 mg, 0.62 mmol), 3-methoxydihydro-2H-pyran-4(3H)-one (242 mg, 1.86 mmol), 4 Å molecular sieves (0.3 g) and TEA (0.259 mL, 1.86 mmol) in DCM (8 mL) was stirred at rt for 2 h, followed by addition of sodium triacetoxyborohydride (263 mg, 1.24 mmol). The resulting mixture was stirred at rt overnight. The reaction was quenched by the addition of saturated NaHCO3 aqueous solution, extracted with DCM, and dried over Na2SO4. After removal of the solvent, the residue was purified by column chromatography (eluent: EtOAc to 15% 7N NH3 in methanol in EtOAc) to give the product as a white foam. 1H-NMR (400 MHz, CDCl3): δ 1.76 (br. s., 1H), 1.89-2.41 (m, 4H), 2.53 (br. s., 1H), 2.85-2.99 (m, 2H), 3.06-4.02 (m, 18H), 4.12 (q, J=7.1 Hz, 1H), 4.69 (br. s., 2H), 5.17-5.31 (m, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.34-7.49 (m, 2H); LC/MS: C25H33F3N4O4: m/z 511.0 (M+H).

Workup

  1. stirringThe resulting mixture was stirred at rt overnight
  2. customThe reaction was quenched by the addition of saturated NaHCO3 aqueous solution
  3. extractionextracted with DCM
  4. dry with materialdried over Na2SO4
  5. customAfter removal of the solvent
  6. customthe residue was purified by column chromatography (eluent: EtOAc to 15% 7N NH3 in methanol in EtOAc)

Sources & evidence

ORD record
ord-fa53d4cb156745c7bc717405fb31db8e
Source dataset
uspto-grants-2015_05
Patent number
US09024017B2

Reaction notes

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