Water → HCID 178473808, compound

HRID 2053926Notes

Reaction equation

HRID 2053926 reaction equation
[Cl:1][C:2]1[CH:34]=[CH:33][C:5]2[NH:6][C:7]([CH:9]([CH:27]3[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]3)[NH:10][C:11](=[O:26])[C:12]3[CH:17]=[CH:16][C:15]([C:18]([N:20]4[CH2:24][CH2:23][CH2:22][CH2:21]4)=[O:19])=[C:14]([CH3:25])[CH:13]=3)=[N:8][C:4]=2[CH:3]=1.[H-].[Na+].[C:37](Cl)(=[O:39])[CH3:38].O>O1CCCC1>[C:37]([N:29]1[CH2:30][CH2:31][CH2:32][CH:27]([CH:9]([C:7]2[NH:6][C:5]3[CH:33]=[CH:34][C:2]([Cl:1])=[CH:3][C:4]=3[N:8]=2)[NH:10][C:11](=[O:26])[C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[O:19])=[C:14]([CH3:25])[CH:13]=2)[CH2:28]1)(=[O:39])[CH3:38]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 24758Sodium hydrideHCID 178427017HCID 178427017, compound

Product 1

HCID 178473808HCID 178473808, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

90 mg (0.16 mmol) of rac.-N-[(5-chloro-1H-benzimidazol-2-yl)-(piperidin-3-yl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide is dissolved in 3 mL of tetrahydrofuran and, after the addition of 8.4 mg (0.17 mmol) of sodium hydride (50% solution in oil), stirred for one hour at 40° C. Then the mixture is cooled to ambient temperature and stirred for a further 16 hours with 11.4 μL (0.16 mmol) of acetyl chloride. Then water is added and the mixture is extracted with dichloromethane. The combined organic extracts are dried over sodium sulfate and concentrated by evaporation. The residue is chromatographed on silica gel, eluting with dichloromethane/ethanol (100:0 and 90:10). The 4 possible stereoisomers were separated into one pair of enantiomers with a high Rf value (Example 189) and one pair of enantiomers with a low Rf value (Example 190). Yield: 30 mg (36% of theory); Rf value: 0.37 (silica gel; dichloromethane/ethanol=9:1); C28H32ClN5O3 (522.05); mass spectrum: (M+H)+=522/524 (chlorine isotope).

Workup

  1. temperatureThen the mixture is cooled to ambient temperature
  2. extractionthe mixture is extracted with dichloromethane
  3. dry with materialThe combined organic extracts are dried over sodium sulfate
  4. concentrationconcentrated by evaporation
  5. customThe residue is chromatographed on silica gel
  6. washeluting with dichloromethane/ethanol (100:0 and 90:10)
  7. customThe 4 possible stereoisomers were separated into one pair of enantiomers with a high Rf value (Example 189) and one pair of enantiomers with a low Rf value (Example 190)

Sources & evidence

ORD record
ord-b211437e03554263be2a3e4f3508ddd0
Source dataset
uspto-grants-2008_02
Patent number
US07326791B2

Reaction notes

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