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

HRID 2064205Notes

Reaction equation

HRID 2064205 reaction equation
Cl.[Cl:2][C:3]1[C:4]([CH3:19])=[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]([CH3:19])=[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 691281886-Chloro-5-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Product 1

HCID 160710146-chloro-5-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

6-Chloro-5-methyl-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D9) (˜0.2 mmol, 60 mg), Ti(iPrO)4 (2 eq., 0.400 mmol, 0.130 ml), tetrahydro-4H-pyran-4-one (2 eq., 0.400 mmol, 40 ul) were stirred together at room temperature for one hour; dry MeOH (2 ml) followed by NaBH3CN (2 eq., ˜30 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-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, 10 mg, 14%, M++H=350, 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-4b5b942c28c24a2e836451d65691894c
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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