Tetrahydro-4H-pyran-4-one → 5-chloro-6-methoxy-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

HRID 2064211Notes

Reaction equation

HRID 2064211 reaction equation
Cl.[CH3:2][O:3][C:4]1[C:5]([Cl:20])=[CH:6][C:7]2[NH:11][C:10](=[O:12])[N:9]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:8]=2[CH:19]=1.[O:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1.[BH3-]C#N.[Na+]>CO>[Cl:20][C:5]1[C:4]([O:3][CH3:2])=[CH:19][C:8]2[N:9]([CH:13]3[CH2:14][CH2:15][N:16]([CH:24]4[CH2:25][CH2:26][O:21][CH2:22][CH2:23]4)[CH2:17][CH2:18]3)[C:10](=[O:12])[NH:11][C:7]=2[CH:6]=1

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 691284086-Methoxy-5-chloro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Product 1

HCID 160711315-chloro-6-methoxy-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-Methoxy-5-chloro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D50) (30 mg, 0.1 mmol), Ti(iPrO)4 (0.15 ml, 0.5 mmol), and tetrahydro-4H-pyran-4-one (50 mg, 0.5 mmol) were stirred together at room temperature for 1 h; dry methanol (1 ml) followed by NaBH3CN (30 mg, 0.5 mmol) were added and the mixture was stirred at room temperature for 2 h. The crude mixture was then quenched with methanol and it was purified first by SCX column chromatography followed by silica gel chromatography (10% methanol-NH3-dichloromethane) to afford 5-chloro-6-methoxy-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one. Conversion to the hydrochloride gave the title compound, 10 mg, MH+=366 and 368.

Workup

  1. additionwere added
  2. customThe crude mixture was then quenched with methanol and it
  3. customwas purified first by SCX column chromatography

Sources & evidence

ORD record
ord-e1752987a3ed478dbe8ab6c6dc8633ff
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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