Tetrahydro-4H-pyran-4-one → HCID 16038387, compound

HRID 2064204Notes

Reaction equation

HRID 2064204 reaction equation
Cl.[Cl:2][C:3]1[C:4]([F:19])=[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>[Cl:2][C:3]1[C:4]([F:19])=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:13][CH2:14][N:15]([CH:23]4[CH2:24][CH2:25][O:20][CH2:21][CH2:22]4)[CH2:16][CH2:17]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 16038387HCID 16038387, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-Chloro-5-fluoro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D5) (0.286 mmol, 77 mg), Ti(iPrO)4 (2 eq., 0.572 mmol, 0.170 ml), tetrahydro-4H-pyran-4-one (2 eq., 0.572 mmol, 0.053 ml) were stirred together at room temperature for one hour; dry methanol (2 ml) followed by NaBH3CN (2 eq., 0.572 mmol, 36 mgs) were added and the mixture was stirred under argon at room temperature for 3 hours. The crude mixture was subsequently quenched with water (5 ml) and it was firstly purified by SCX followed by chromatography (methanol-NH3-dichloromethane) to yield 6-chloro-5-fluoro-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 15 mg, 13%, M++H=353, which was converted into the hydrochloride salt using 1M HCl in diethyl ether.

Workup

  1. additionwere added
  2. customThe crude mixture was subsequently quenched with water (5 ml) and it
  3. customwas firstly purified by SCX

Sources & evidence

ORD record
ord-ed8fd44398dd4ef4a1f3a2bce0c5bccc
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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