Water → 2-Chloro-N-[(6R,7aS)-3-oxo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-6-yl]-benzamide

HRID 455258Notes

Reaction equation

HRID 455258 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](Cl)=[O:5].[NH2:11][C@H:12]1[CH2:31][N:15]2[C:16](=[O:30])[N:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[CH:21][CH:20]=3)[CH2:18][C@@H:14]2[CH2:13]1.CCN(C(C)C)C(C)C.O>ClCCl>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:11][C@H:12]1[CH2:31][N:15]2[C:16](=[O:30])[N:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:27])[F:28])=[CH:21][CH:20]=3)[CH2:18][C@@H:14]2[CH2:13]1)=[O:5]

Participants

6

Reactant 4

HCID 962WaterHCID 691102-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 70976166(6R,7aS)-6-Amino-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one

Product 1

HCID 709762012-Chloro-N-[(6R,7aS)-3-oxo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-6-yl]-benzamideYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Chloro-benzoyl chloride (40.5 mg, 0.23 mmol) was dropped into a solution of (6R,7aS)-6-Amino-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one (70 mg, 0.23 mmol) and DIPEA (23 mg, 0.23 mmol) in anhydrous dichloromethane (3 mL), the mixture was stirred at room temperature for 4 hours. Then the mixture was poured into water (10 mL) extracted with ethyl acetate (3×10 mL), the organic layers was combined, washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=5:1) to give 85 mg (83%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.70-7.67 (m, 1H), 7.60 (d, 2H, J=9.3 Hz), 7.43-7.32 (m, 3H), 7.20 (d, 2H, J=9.0 Hz), 6.49 (d, 1H, J=6.6 Hz), 4.76-4.68 (m, 1H), 4.26 (dd, 1H, J1=12.6 Hz, J2=7.2 Hz), 4.18-4.02 (m, 2H), 3.76 (dd, 1H, J1=9 Hz, J2=2.1 Hz), 3.13 (dd, 1H, J1=12.9 Hz, J2=3.3 Hz), 2.35-2.28 (m, 1H), 1.93-1.83 (m, 1H); LC-MS: 440.1 [M+1]+.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. washwashed with brine (20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate=5:1)

Sources & evidence

ORD record
ord-91b73a567bd14dae9eddbd11e859e501
Source dataset
uspto-grants-2013_07
Patent number
US08497288B2

Reaction notes

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