Water → methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-1H-benzimidazole-6-carboxylate

HRID 1691744Notes

Reaction equation

HRID 1691744 reaction equation
Cl[C:2]1[NH:6][C:5]2[CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=[CH:10][C:4]=2[N:3]=1.[F:15][C:16]1[CH:17]=[C:18]([CH:22]2[CH:27]([CH2:28][N:29]([C@@H:37]([C:39]3[C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[CH:42]=[CH:41][CH:40]=3)[CH3:38])[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[CH2:26][CH2:25][NH:24][CH2:23]2)[CH:19]=[CH:20][CH:21]=1.O>CS(C)=O>[C:32]([O:31][C:30]([N:29]([CH2:28][CH:27]1[CH2:26][CH2:25][N:24]([C:2]2[NH:6][C:5]3[CH:7]=[C:8]([C:11]([O:13][CH3:14])=[O:12])[CH:9]=[CH:10][C:4]=3[N:3]=2)[CH2:23][CH:22]1[C:18]1[CH:19]=[CH:20][CH:21]=[C:16]([F:15])[CH:17]=1)[C@@H:37]([C:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH:42]=[CH:41][CH:40]=1)[CH3:38])=[O:36])([CH3:33])([CH3:34])[CH3:35]

Participants

5

Reactant 3

HCID 962WaterHCID 11543028Methyl 2-chloro-1H-benzo[d]imidazole-5-carboxylateHCID 59178728tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate

Product 1

HCID 66905807methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-1H-benzimidazole-6-carboxylateYield 34.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 313 mg of methyl 2-chloro-1H-benzimidazole-6-carboxylate and 100 mg of tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate in 2.00 mL of DMSO was stirred at 130° C. for 9 hours. The reaction mixture was cooled to room temperature, and water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 48 mg of methyl 2-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-1H-benzimidazole-6-carboxylate as a pale yellow solid. ESI+: 637

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-7135e57c40114ab8b7252179bb0af293
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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