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

HRID 1479818Notes

Reaction equation

HRID 1479818 reaction equation
[CH3:1][N:2]([S:8]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)(=[O:10])=[O:9])[C:3](=[CH2:7])[C:4]([OH:6])=O.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>[CH3:1][N:2]([S:8]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)(=[O:10])=[O:9])[C:3](=[CH2:7])[C:4]([NH:45][CH2:44][C:42]1[CH:41]=[CH:40][N:39]=[C:38]([C:35]2[CH:34]=[CH:33][C:32]([O:31][C:30]([F:47])([F:29])[F:46])=[CH:37][CH:36]=2)[CH:43]=1)=[O:6]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68759664[2-[4-(Trifluoromethoxy)phenyl]-4-pyridyl]methanamineHCID 903842282-(Methyl(p-tolylsulfonyl)amino)prop-2-enoic acid

Product 1

HCID 903842092-(methyl(p-tolylsulfonyl)amino)-N-[[2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4E (0.57 g, 2.2 mmol) in THF (30 mL) was added with DEPC (0.43 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 (0.66 g, 1.1 mol eq) and a catalytic amount of TEA were added, then the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, the residue was suspended in EtOAc and washed with water and brine. The separated organic phase was evaporated under reduced pressure and the residue was purified by flash chromatography (7:3 EtOAc:Petroleum ether) to afford a pale yellow solid (0.27 g) after crystallization from a mixture of diethyl ether/petroleum ether. Yield=25%, 1HNMR (DMSO, 200 MHz) δ 2.48 (s, 3H), 2.86 (s, 3H), 4.49 (d, 2H, J=6), 5.00 (s, 1H), 5.85 (s, 1H), 7.35 (d, 1H), 7.42 (m, 4H), 7.71 (d, 2H, J=8.2), 7.97 (s, 1H), 8.21 (dd, 2H, J=2.2), 8.61 (d, 1H, J=4), 8.90 (t, 1H); [M+1] 505.51 (C24H22F3N3O4S requires 505.12).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. washwashed with water and brine
  4. customThe separated organic phase was evaporated under reduced pressure
  5. customthe residue was purified by flash chromatography (7:3 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-4aad5fa7fe9e42939fc522c275eb8e65
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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