Diethyl Pyrocarbonate → 2-[ethyl-(3,4-difluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamide

HRID 1479861Notes

Reaction equation

HRID 1479861 reaction equation
[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[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:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([F:19])[CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([NH:46][CH2:45][C:43]1[CH:42]=[CH:41][N:40]=[C:39]([C:36]2[CH:37]=[CH:38][C:33]([C:32]([F:48])([F:31])[F:47])=[CH:34][CH:35]=2)[CH:44]=1)=[O:7])[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68758847[2-(4-Trifluoromethyl-phenyl)-pyridin-4-yl]methylamineHCID 903905002-[Ethyl-(3,4-difluorophenyl)sulfonyl-amino]prop-2-enoic acid

Product 1

HCID 903903852-[ethyl-(3,4-difluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acid 4G (500 mg, 1.7 mmol) was dissolved in 20 ml of THF and at rt DEPC (1.3 equiv, 0.34 ml) and [2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 21A (1.1 equiv., 476 mg) were added to the solution. The mixture was stirred at rt overnight then evaporated. The 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 (EtOAc 1/petroleum ether 1) afforded 120 mg of a white solid. Yield=24% 1HNMR (DMSO, 200 MHz) δ 1.09 (3H, t, J=7.2 Hz), 3.45 (2H, q, J=6.8 Hz), 4.51 (2H, d, J=6 Hz), 5.31 (1H, s), 6.17 (1H, s), 7.38 (1H, dd, J=4.8 Hz, J′=1.2 Hz), 7.68 (2H, t, J=8.8 Hz), 7.83 (d, 3H), 8.02 (s, 1H), 8.32 (d, 2H, J=7.8), 8.67 (d, 1H, J=5.8), 8.93 (t, 1H). [M+1] 525.11 (C24H20F5N3O3S requires 524.98).

Workup

  1. additionwere added to the solution
  2. customthen evaporated
  3. dissolutionThe 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 (EtOAc 1/petroleum ether 1)

Sources & evidence

ORD record
ord-63a78c1cc4b04c39b89d74612917eccc
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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