Diethyl Pyrocarbonate → (Z)-2-[methyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]but-2-enamide

HRID 1479840Notes

Reaction equation

HRID 1479840 reaction equation
[CH3:1][N:2]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])/[C:3](=[CH:7]\[CH3:8])/[C:4]([OH:6])=O.CCOC(OC(OCC)=O)=O.[F:30][C:31]([F:48])([F:47])[O:32][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>[CH3:1][N:2]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])/[C:3](=[CH:7]\[CH3:8])/[C:4]([NH:46][CH2:45][C:43]1[CH:42]=[CH:41][N:40]=[C:39]([C:36]2[CH:35]=[CH:34][C:33]([O:32][C:31]([F:48])([F:30])[F:47])=[CH:38][CH:37]=2)[CH:44]=1)=[O:6]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68759664[2-[4-(Trifluoromethoxy)phenyl]-4-pyridyl]methanamineHCID 90384222(Z)-2-[methyl-(4-fluorophenyl)sulfonyl-amino]but-2-enoic acid

Product 1

HCID 78321165(Z)-2-[methyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]but-2-enamideYield 15.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acid 11A (515 mg, 2.5 mmol) was dissolved in 10 ml of THF and at rt DEPC (1.1 equiv, 0.38 ml) and [2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine 21B (1.1 equiv., 737 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 (1:1 EtOAc:petroleum ether) afforded 200 mg of a pale yellow solid. Yield=15% 1HNMR (DMSO, 200 MHz) δ 1.74 (3H, d J=7.4 Hz), 3.06 (3H, s), 4.40 (2H, d, J=6 Hz), 6.83 (1H, q, J=7 Hz), 7.44 (5H, m), 7.83 (3H, m), 8.18 (2H, d, J=8.2 Hz), 8.59 (1H, d, J=5.2 Hz), 8.70 (1H, bt) [M+1] 524.3 (C24H21F4N3O4S requires 523.50).

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 (1:1 EtOAc:petroleum ether)

Sources & evidence

ORD record
ord-eccc207441334c90a7580a2ffa13a857
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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