Acetone Cyanohydrin → 4-[4-(5-Fluoro-6-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]tetrahydro-2H-pyran-4-carbonitrile

HRID 2064176Notes

Reaction equation

[F:1][C:2]1[C:17]([CH3:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.O[C:20]([CH3:24])([CH3:23])[C:21]#[N:22].[O:25]1[CH2:30]CC(=O)C[CH2:26]1>CC(N(C)C)=O>[F:1][C:2]1[C:17]([CH3:18])=[CH:16][C:5]2[N:6]([CH:10]3[CH2:11][CH2:12][N:13]([C:20]4([C:21]#[N:22])[CH2:24][CH2:30][O:25][CH2:26][CH2:23]4)[CH2:14][CH2:15]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 5-fluoro-6-methyl-1-piperidin-4-yl-1,3-dihydro-2H-benzimidazol-2-one (D30, 0.6 g, 2.4 mmol), 2-hydroxy-2-methylpropanenitrile, (380 mg, 4.8 mmol), tetrahydro-4H-pyran-4-one (480 mg) magnesium sulphate (1.4 g) and N,N-dimethylacetamide (2.4 ml) were stirred at 65° C. under a slow stream of argon. Extra 2 ml DMA was added and stirred for a further 4 hours. The mixture was partitioned between dichloromethane and water. The dichloromethane layer was separated, dried by passing through a 3 g hydromatrix cartridge. The solvent was removed and the title compound was obtained as a off white solid from ether (617 mg). M+ 359.

Workup

stirringstirred for a further 4 hours
customThe mixture was partitioned between dichloromethane and water
customThe dichloromethane layer was separated
customdried
customThe solvent was removed

Sources & evidence

ORD record: ord-24f91b46f3b543af927b257f78653679
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08288412B2

Reaction notes

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