Diethyl Pyrocarbonate → 1-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide

HRID 1479846Notes

Reaction equation

HRID 1479846 reaction equation
[CH2:1]([N:3]([S:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[C:4]1([C:7]([OH:9])=O)[CH2:6][CH2:5]1)[CH3:2].CCOC(OC(OCC)=O)=O.[F:31][C:32]([F:48])([F:47])[C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[C:43]([CH2:45][NH2:46])[CH:42]=[CH:41][N:40]=2)=[CH:35][CH:34]=1>C1COCC1>[CH2:1]([N:3]([S:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[C:4]1([C:7]([NH:46][CH2:45][C:43]2[CH:42]=[CH:41][N:40]=[C:39]([C:36]3[CH:37]=[CH:38][C:33]([C:32]([F:48])([F:31])[F:47])=[CH:34][CH:35]=3)[CH:44]=2)=[O:9])[CH2:5][CH2:6]1)[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68758847[2-(4-Trifluoromethyl-phenyl)-pyridin-4-yl]methylamineHCID 903843631-[Ethyl-(4-fluorophenyl)sulfonyl-amino]cyclopropanecarboxylic acid

Product 1

HCID 903841851-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamideYield 26.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acid 15A (303 mg, 1 mmol) was dissolved in 5 ml of THF and at rt DEPC (1.1 equiv, 0.17 ml) and [2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 21A (1.1 equiv., 277.5 mg) were added to the solution. The mixture was stirred at rt overnight then evaporated. he residue was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude by chromatographic column (1:1 EtOAc:Petroleum ether) afforded 140 mg of a white solid. Yield=26.8% 1HNMR (DMSO, 400 MHz) δ 1.09 (2H, bs), 1.23 (3H, t, J=7.2 Hz), 1.40 (2H, bs), 3.40 (2H, q, J=6.8 Hz), 4.41 (2H, bs), 7.26 (1H, dd), 7.42 (2H, t, J=8.8 Hz), 7.87 (4H, m), 7.98 (1H, bs), 8.30 (3H, bd), 8.64 (1H, dd, J=4.8 Hz) [M+1] 521.9 (C25H23F4N3O3S requires 521.53).

Workup

  1. additionwere added to the solution
  2. customthen evaporated
  3. dissolutionhe residue was dissolved in AcOEt (30 ml)
  4. washwashed with water (1×20 ml) and brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe purification of the crude by chromatographic column (1:1 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-40b66184ffaf4aba94adb4a358c76b95
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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