Cesium carbonate → 3-(4-Chlorophenyl)-N-(2,2-dimethyl-propyl)-1-[(4-fluorophenyl)-methyl]-N-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylic acid amide

HRID 623788Notes

Reaction equation

HRID 623788 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[NH:10][C:9]=2[C:17]([N:19]([CH3:25])[CH2:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:18])=[CH:4][CH:3]=1.Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([C:13]([F:15])([F:16])[F:14])[N:10]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[C:9]=2[C:17]([N:19]([CH2:20][C:21]([CH3:22])([CH3:24])[CH3:23])[CH3:25])=[O:18])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 680214-Fluorobenzyl bromideHCID 867118723-(4-Chlorophenyl)-N-methyl-N-neopentyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide

Product 1

HCID 867118733-(4-Chlorophenyl)-N-(2,2-dimethyl-propyl)-1-[(4-fluorophenyl)-methyl]-N-methyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-(4-chlorophenyl)-N-methyl-N-neopentyl-5-(trifluoromethyl)-1H-pyrrole-2-carboxamide (100 mg, 0.268 mmol) in dry DMF (1.5 mL) was added 1-(bromomethyl)-4-fluorobenzene (35 μL, 0.282 mmol) and Cs2CO3(131 mg, 0.402 mmol). The white suspension was stirred at 60° C. for 1 h. The reaction mixture was poured out in saturated aqueous NaHCO3 (25 mL) and the product was extracted with EtOAc (2×25 mL). The combined organic layers were washed with saturated aqueous NaHCO3 (2×15 mL), aqueous 1M KHSO4 (2×15 mL) and brine (2×15 mL) before drying on Na2SO4 and concentration in vacuo. The product was purified using flash chromatography (silica, gradient heptane/EtOAc 95:5→7:3). The product containing fractions were combined, concentrated in vacuo and crystallised from hot i-Pr2O to give a first batch of SC-261. The mother liquor was concentrated in vacuo and crystallised from i-Pr2O/heptane (1:1) to give white crystals which were combined with the earlier obtained batch to give SC-261 (58 mg, 45%) as colorless crystals.

Workup

  1. extractionthe product was extracted with EtOAc (2×25 mL)
  2. washThe combined organic layers were washed with saturated aqueous NaHCO3 (2×15 mL), aqueous 1M KHSO4 (2×15 mL) and brine (2×15 mL)
  3. custombefore drying on Na2SO4 and concentration in vacuo
  4. customThe product was purified
  5. additionThe product containing fractions
  6. concentrationconcentrated in vacuo
  7. customcrystallised from hot i-Pr2O

Sources & evidence

ORD record
ord-a4908847e8d1428d97f304ffd5a94855
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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