4-{4-[6-Chloro-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrile → 6-Chloro-1-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 2064216Notes

Reaction equation

HRID 2064216 reaction equation
[Cl:1][C:2]1[C:3]([C:26]([F:29])([F:28])[F:27])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]4([C:23]#N)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[CH2:13][CH2:12]3)[C:6]=2[CH:25]=1.C[Mg]Br>O1CCCC1>[ClH:1].[Cl:1][C:2]1[C:3]([C:26]([F:27])([F:28])[F:29])=[CH:4][C:5]2[NH:9][C:8](=[O:10])[N:7]([CH:11]3[CH2:12][CH2:13][N:14]([C:17]4([CH3:23])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)[CH2:15][CH2:16]3)[C:6]=2[CH:25]=1

Participants

4

Reactant 2

HCID 598501594-{4-[6-Chloro-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrileHCID 178418573HCID 178418573, compound

Product 1

HCID 691279036-Chloro-1-[1-(4-methyltetrahydro-2H-pyran-4-yl)-4-piperidinyl]-5-(trifluoromethyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-{4-[6-chloro-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrile (D65, 1160 mg, 0.37 mmol) in tetrahydrofuran (5 ml) was treated with methylmagnesium bromide (3M in diethyl ether, 1.0 ml, 3.0 mmol). After 2 h at room temperature the solution was partitioned between aqueous Rochelle salt solution and dichloromethane, and the organic layer was dried (MgSO4) and evaporated The residue was chromatographed on silica gel eluting with methanol-dichloromethane mixtures to afford the title compound, which was isolated as the hydrochloride salt triturated from diethyl ether (110 mg). MH+=418 and 420,

Workup

  1. customAfter 2 h at room temperature the solution was partitioned between aqueous Rochelle salt solution and dichloromethane
  2. dry with materialthe organic layer was dried (MgSO4)
  3. customevaporated The residue
  4. customwas chromatographed on silica gel eluting with methanol-dichloromethane mixtures

Sources & evidence

ORD record
ord-c2452bea3fac42b88d5063779ee0a739
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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