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

HRID 1479808Notes

Reaction equation

HRID 1479808 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH3:17])[C:12](=[CH2:16])[C:13]([OH:15])=O)(=[O:10])=[O:9])=[CH:4][CH:3]=1.CCOC(OC(OCC)=O)=O.[F:29][C:30]([F:47])([F:46])[O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[C:42]([CH2:44][NH2:45])[CH:41]=[CH:40][N:39]=2)=[CH:34][CH:33]=1>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH3:17])[C:12](=[CH2:16])[C:13]([NH:45][CH2:44][C:42]2[CH:41]=[CH:40][N:39]=[C:38]([C:35]3[CH:34]=[CH:33][C:32]([O:31][C:30]([F:47])([F:29])[F:46])=[CH:37][CH:36]=3)[CH:43]=2)=[O:15])(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68759664[2-[4-(Trifluoromethoxy)phenyl]-4-pyridyl]methanamineHCID 1317365812-[(4-Fluorophenyl)sulfonyl-methyl-amino]prop-2-enoic acid

Product 1

HCID 783199112-[(4-fluorophenyl)sulfonyl-methyl-amino]-N-[[2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4A (0.26 g, 1 mmol) in THF (25 mL) was added with DEPC (0.18 mL, 1.3 mol eq) and the mixture was stirred at room temperature for about 5 minutes. Then [2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methanamine 21B (0.27 g, 1.1 mol eq) and a catalytic amount of TEA were added. The reaction mixture was then stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue was suspended in EtOAc (30 mL) and washed with water (50 mL) and brine. The separated organic phase, after drying over Na2SO4, was evaporated under reduced pressure and the residue was purified by flash chromatography (8:2 EtOAc:Petroleum ether) to afford a pale yellow solid (0.1 g) after crystallization from a mixture of diethyl ether/petroleum ether. Yield=23%, 1HNMR (DMSO, 200 MHz) δ 2.95 (3H, s), 4.49 (d, 2H, J=6 Hz), 5.10 (s, 1H), 5.88 (s, 1H), 7.35 (dd, 1H), 7.47 (m, 4H), 7.48 (m, 2H), 7.96 (s, 1H), 8.21 (dd, 2H), 8.61 (d, 1H, J=4 Hz), 8.94 (t, 1H); [M+1] 509.47 (C23H19F4N3O4S requires 509.10).

Workup

  1. stirringThe reaction mixture was then stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. washwashed with water (50 mL) and brine
  4. dry with materialThe separated organic phase, after drying over Na2SO4
  5. customwas evaporated under reduced pressure
  6. customthe residue was purified by flash chromatography (8:2 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-8fb44f40288c46a29296830a25ad6756
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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