Triethylamine → HCID 59850144, compound

HRID 2064206Notes

Reaction equation

HRID 2064206 reaction equation
Cl.[Cl:2][C:3]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][C:6]2[N:7]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[C:8](=[O:10])[NH:9][C:5]=2[CH:4]=1.C(N(CC)CC)C.[O:30]1[CH2:35][CH2:34][C:33](=O)[CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.ClCCCl>[Cl:2][C:3]1[C:18]([C:19]([F:20])([F:21])[F:22])=[CH:17][C:6]2[N:7]([CH:11]3[CH2:16][CH2:15][N:14]([CH:33]4[CH2:34][CH2:35][O:30][CH2:31][CH2:32]4)[CH2:13][CH2:12]3)[C:8](=[O:10])[NH:9][C:5]=2[CH:4]=1

Participants

7

Reactant 4

HCID 8471Triethylamine3×HCID 121599Tetrahydro-4H-pyran-4-one3×HCID 5049666Sodium triacetoxyborohydride3×HCID 69237227HCID 69237227, compound

Product 1

HCID 59850144HCID 59850144, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

5-Chloro-1-(4-piperidinyl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (0.228 mmol, 82 mg) was dissolved in dichloromethane (6 ml) and triethylamine (3 eq., 0.68 mmol, 50 microliters), tetrahydro-4H-pyran-4-one (7 eq., 1.6 mmol, 160 mg), sodium triacetoxyborohydride (7 eq., 1.6 mmol, 340 mg) were added at room temperature and the mixture was stirred at room temperature for 3 hours. More triethylamine (4 ml), tetrahydro-4H-pyran-4-one (3.5 eq, 0.8 mmol, 80 mg), sodium triacetoxyborohydride (3.5 eq, 0.8 mmol, 170 mg) were added at room temperature and the mixture was stirred at room temperature for two extra hours. The solvent was evaporated and the mixture was worked up with sodium bicarbonate and DCM. The solvent was evaporated and triethylamine (3 eq., 0.68 mmol, 50 microliters), tetrahydro-4H-pyran-4-one (7 eq, 1.6 mmol, 160 mg), sodium triacetoxyborohydride (7 eq, 1.59 mmol, 340 mg) and DCE (4 ml) were introduced and all mixed together for 1 hour at room temperature. The mixture was quenched with water/NaHCO3 (saturated solution) and DCM. 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 (MeOH—NH3-dichloromethane) to afford 5-chloro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-6-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one, 29 mg, 31%, M++H=403, which was subsequently converted into the mono-hydrochloride salt using HCl (2 eq. from a 1M solution of HCl in diethyl ether).

Workup

  1. stirringthe mixture was stirred at room temperature for two extra hours
  2. customThe solvent was evaporated
  3. customThe solvent was evaporated
  4. additionall mixed together for 1 hour at room temperature
  5. customThe mixture was quenched with water/NaHCO3 (saturated solution) and DCM
  6. customThe organic phase was separated from the aqueous phase (by hydrophobic filters)
  7. customthe organic solvent was evaporated
  8. customto afford the crude product that
  9. customwas purified by chromatography (MeOH—NH3-dichloromethane)

Sources & evidence

ORD record
ord-0f3aa342ad0546f9b0b89eaa693e6560
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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