Tetrahydro-4H-pyran-4-one → HCID 69122355, compound

HRID 2064088Notes

Reaction equation

HRID 2064088 reaction equation
Cl.[Cl:2][C:3]1[C:4](F)=[CH:5][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.[O:20]1[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]1.[BH3-]C#N.[Na+]>CO>[ClH:2].[Cl:2][C:3]1[CH:4]=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:17][CH2:16][N:15]([CH:23]4[CH2:24][CH2:25][O:20][CH2:21][CH2:22]4)[CH2:14][CH2:13]3)[C:7]=2[CH:18]=1

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 69122553HCID 69122553, compound

Product 1

HCID 69122355HCID 69122355, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-Chloro-5-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (2.0 g), Ti(iPrO)4 (4.2 mL), and tetrahydro-4H-pyran-4-one (1.4 g) were stirred together at room temperature for 1 h; dry methanol (30 mL) followed by NaBH3CN (0.8 g) were added and the mixture was stirred at room temperature for 1 h. The crude mixture was then quenched with methanol and it was purified first by SCX column chromatography followed by filtration and silica gel chromatography (methanol-NH3-dichloromethane). Conversion to the hydrochloride gave the title compound, 950 mg, MH+=336 and 338, 1H NMR (HCl salt) (DMSO-d6) 1.72 (2H, m), 1.94 (2H, m), 2.03 (2H, m), 2.81 (2H, m), 3.20 (2H, m), 3.33 (2H, m), 3.44 (1H, m), 4.01 (2H, m), 4.61 (1H, m), 7.02 (2H, m), 7.66 (1H, s), 10.52 (1H, bs) and 11.12 (1H, s).

Workup

  1. additionwere added
  2. customThe crude mixture was then quenched with methanol and it
  3. customwas purified first by SCX column chromatography
  4. filtrationfollowed by filtration and silica gel chromatography (methanol-NH3-dichloromethane)

Sources & evidence

ORD record
ord-ff4dc076c9fa478ea1162daf8d06d520
Source dataset
uspto-grants-2012_10
Patent number
US08288413B2

Reaction notes

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