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

HRID 2061507Notes

Reaction equation

HRID 2061507 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([F:19])[C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:7]=2[CH:18]=1.C(N(CC)CC)C.[O:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:2][C:3]1[CH:4]=[C:5]([F:19])[C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:13][CH2:14][N:15]([CH:30]4[CH2:31][CH2:32][O:27][CH2:28][CH2:29]4)[CH2:16][CH2:17]3)[C:7]=2[CH:18]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 121599Tetrahydro-4H-pyran-4-one2×HCID 5049666Sodium triacetoxyborohydride2×HCID 686243266-Chloro-4-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Product 1

HCID 160692196-chloro-4-fluoro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

6-Chloro-4-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride D9 (0.36 mmol, 0.1 g) was dissolved in dichloromethane (10 ml) and triethylamine (3 eq., 1.08 mmol, 80 microliters), tetrahydro-4H-pyran-4-one (4.5 eq., 1.62 mmol, 162 mg), sodium triacetoxyborohydride (4.5 eq., 1.62 mmol, 345 mg) were added at room temperature and the mixture was stirred at room temperature for 2 hours. Additional tetrahydro-4H-pyran-4-one (2 eq., 0.72 mmol, 72 microliters) and sodium triacetoxyborohydride (2 eq., 0.72 mmol, 0.015 g) were added at room temperature and the mixture was stirred at room temperature for two further hours. The mixture was quenched with water and brought to pH≈10 by sodium hydroxide (aqueous solution). The organic phase was separated from the aqueous phase (by hydrophobic filters) and the organic solvent was evaporated to afford the crude product that was purified by chromatography (methanol-NH3-dichloromethane) to afford 6-chloro-4-fluoro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 15 mg, 11%, M++H=354 and 356, which was converted to the hydrochloride salt using 1M HCl in diethyl ether.

Workup

  1. stirringthe mixture was stirred at room temperature for two further hours
  2. customThe mixture was quenched with water
  3. customThe organic phase was separated from the aqueous phase (by hydrophobic filters)
  4. customthe organic solvent was evaporated
  5. customto afford the crude product that
  6. customwas purified by chromatography (methanol-NH3-dichloromethane)

Sources & evidence

ORD record
ord-484a8307b72b4b9b9e11dea36b8f8e2c
Source dataset
uspto-grants-2012_10
Patent number
US08283364B2

Reaction notes

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