Dimethylcarbamoyl Chloride → 4-(2,5-difluorophenyl)-N,N-dimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide

HRID 1394912Notes

Reaction equation

HRID 1394912 reaction equation
C(N(CC)CC)C.[CH3:8][N:9]([CH3:13])[C:10](Cl)=[O:11].[F:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[C:22]1[CH2:26][NH:25][CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:23]=1>ClCCl>[F:14][C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=1[C:22]1[CH2:26][N:25]([C:10]([N:9]([CH3:13])[CH3:8])=[O:11])[CH:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:23]=1

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 590017764-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole

Product 1

HCID 104042254-(2,5-difluorophenyl)-N,N-dimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (1.37 mL, 9.79 mmol, 5.00 equiv) and dimethylcarbamoyl chloride (0.180 mL, 1.96 mmol, 1.00 equiv) were added to a solution of 4-(2,5-difluorophenyl)-2-phenyl-2,5-dihydro-1H-pyrrole (24, 1.96 mmol) in dichloromethane (50 mL) at 23° C., and the resulting mixture was stirred for 2 hours, then concentrated. The residue was partitioned between saturated aqueous sodium bicarbonate solution (75 ml) and ethyl acetate (100 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TPA present) to provide 4-(2,5-difluorophenyl)-N,N-dimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (2-5) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.35-7.29 (m, 4H), 7.25 (m, 1H), 7.05 (m, 1H), 7.00 (m, 1H), 6.96 (m, 1H), 6.40 (br s, 1H), 6.13 (m, 1H), 4.88 (ddd, 1H, J=13.7, 5.6, 2.0 Hz), 4.52 (d, 1H, J=13.7 Hz), 2.88 (s, 6H). LRMS m/z (M+H) 329.1 found, 329.1 required.

Workup

  1. concentrationconcentrated
  2. customThe residue was partitioned between saturated aqueous sodium bicarbonate solution (75 ml) and ethyl acetate (100 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse-phase LC (H2O/CH3CN gradient w/0.1% TPA present)

Sources & evidence

ORD record
ord-ccc10afd82de41129750a3caf6ae11da
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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