Triethylamine → 6-Cyclopropyl-4-fluoro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 447797Notes

Reaction equation

HRID 447797 reaction equation
[ClH:1].[CH:2]1([C:5]2[CH:6]=[C:7]([F:21])[C:8]3[NH:12][C:11](=[O:13])[N:10]([CH:14]4[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]4)[C:9]=3[CH:20]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C.[O:29]1[CH2:34][CH2:33][C:32](=O)[CH2:31][CH2:30]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[ClH:1].[CH:2]1([C:5]2[CH:6]=[C:7]([F:21])[C:8]3[NH:12][C:11](=[O:13])[N:10]([CH:14]4[CH2:15][CH2:16][N:17]([CH:32]5[CH2:33][CH2:34][O:29][CH2:30][CH2:31]5)[CH2:18][CH2:19]4)[C:9]=3[CH:20]=2)[CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 686255456-Cyclopropyl-4-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Product 1

HCID 686237886-Cyclopropyl-4-fluoro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

6-Cyclopropyl-4-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D29, 0.28 mmol, 86 mg), was dissolved in 1,2-dichloroethane (3 ml) and triethylamine (3 eq., 0.83 mmol, 0.086 g), tetrahydro-4H-pyran-4-one (7 eq., 1.99 mmol, 0.2 g) and sodium triacetoxyborohydride (3 eq., 0.83 mmol, 0.052 g) were added at room temperature and the mixture was stirred at room temperature for one overnight. The reaction mixture was quenched with NaHCO3 (saturated solution) and diluted with dichloromethane, then the two phases were separated by hydrophobic filter and the aqueous was washed with dichloromethane again. The organic phases were combined and the solvent was evaporated to afford the crude product which was purified by chromatography (methanol-NH3-dichloromethane) to afford the free base of the title compound, 100 mg, 98%, M++H=360. This material was dissolved in methanol (2 ml) and HCl (3 eq., 0.046 ml from a 1M solution in diethyl ether) was added at room temperature and the mixture was stirred at room temperature for 5 minutes. The solvent was subsequently evaporated to afford the title compound, 90 mg, 82%.

Workup

  1. customThe reaction mixture was quenched with NaHCO3 (saturated solution)
  2. additiondiluted with dichloromethane
  3. customthe two phases were separated
  4. filtrationby hydrophobic filter
  5. washthe aqueous was washed with dichloromethane again
  6. customthe solvent was evaporated
  7. customto afford the crude product which
  8. customwas purified by chromatography (methanol-NH3-dichloromethane)

Sources & evidence

ORD record
ord-070e959c554343dcb401ffe4704ea941
Source dataset
uspto-grants-2013_07
Patent number
US08481566B2

Reaction notes

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