Ethyl Acetate → HCID 16071015, compound

HRID 2064213Notes

Reaction equation

HRID 2064213 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[CH2:11][CH2:10]2)[C:5]([NH2:21])=[CH:4][C:3]=1[C:22]([F:25])([F:24])[F:23].[C:26](C1NC=CN=1)(C1NC=CN=1)=[O:27].C(OCC)(=O)C>O1CCCC1>[Cl:1][C:2]1[C:3]([C:22]([F:23])([F:25])[F:24])=[CH:4][C:5]2[NH:21][C:26](=[O:27])[N:8]([CH:9]3[CH2:10][CH2:11][N:12]([CH:15]4[CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[CH2:13][CH2:14]3)[C:6]=2[CH:7]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 5250894Bis-(1H-imidazol-2-YL)-methanone2×HCID 59850188HCID 59850188, compound

Product 1

HCID 16071015HCID 16071015, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 5-chloro-N-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-4-trifluoromethyl-1,2-benzenediamine (D52) (0.34 g, 0.9 mmol) in anhydrous tetrahydrofuran (40 ml) was treated with carbonyl diimidazole (0.29 g, 1.80 mmol)—added in portion over 5 minutes. The mixture was stirred at room temperature under argon for 4 hours. The mixture was warmed to a gentle reflux. After 18 hours, a further 0.29 g, 1.8 mmole of carbonyl diimidazole was added and the mixture maintained at reflux for another 24 hours. The mixture was cooled to room temperature and was treated with ethyl acetate (40 ml) and washed with water and brine then dried over MgSO4 and concentrated to dryness. The residue was purified by silica gel chromatography eluting with 1 to 10% methanol in dichloromethane to afford 6-chloro-5-trifluoromethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one, which was subsequently converted to the hydrochloride salt and isolated as a cream powder. 0.25 g, 73%. MH+=404 and 406

Workup

  1. temperatureThe mixture was warmed to a gentle reflux
  2. waitAfter 18 hours
  3. temperaturethe mixture maintained
  4. temperatureat reflux for another 24 hours
  5. temperatureThe mixture was cooled to room temperature
  6. washwashed with water and brine
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated to dryness
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 1 to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-882f7cbe2d8b4f7193930597a81eda39
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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