Diethyl Pyrocarbonate → 2-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-isopropoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamide

HRID 1479876Notes

Reaction equation

HRID 1479876 reaction equation
[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[CH3:2].CCOC(OC(OCC)=O)=O.[CH:30]([O:33][C:34]1[CH:39]=[C:38]([CH2:40][NH2:41])[CH:37]=[C:36]([C:42]2[CH:47]=[CH:46][C:45]([C:48]([F:51])([F:50])[F:49])=[CH:44][CH:43]=2)[N:35]=1)([CH3:32])[CH3:31]>C1COCC1>[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([NH:41][CH2:40][C:38]1[CH:37]=[C:36]([C:42]2[CH:43]=[CH:44][C:45]([C:48]([F:49])([F:50])[F:51])=[CH:46][CH:47]=2)[N:35]=[C:34]([O:33][CH:30]([CH3:32])[CH3:31])[CH:39]=1)=[O:7])[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 903842012-[Ethyl-(4-fluorophenyl)sulfonyl-amino]prop-2-enoic acidHCID 90390965[2-Isopropoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine

Product 1

HCID 903905372-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-isopropoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4B (300 g, 1.09 mmol) in THF (15 mL) was added with DEPC (0.21 mL, 1.3 mol eq) and the mixture was stirred at room temperature several minutes. Then [2-isopropoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27M (370 mg, 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, water was added to the residue that is extracted with EtOAc (3×30 mL) and washed with brine (1×40 mL). The separated organic phase was dried over Na2SO4, evaporated to dryness and the residue was purified by flash chromatography (3/7 EtOAc/Petroleum ether) to afford a white solid (100 mg) after crystallization from ethyl ether. Yield=18%. 1HNMR (DMSO, 400 MHz) δ 1.08 (t, 3H, J=7.4), 1.26 (d, 6H, J=6.2), 3.39 (q, 2H), 4.40 (d, 2H, J=7.9), 5.13 (s, 1H), 5.39 (m, 1H), 6.12 (s, 1H), 6.65 (s, 1H), 7.42 (t, 3H, J=4), 7.56 (s, 1H), 7.86 (m, 4H), 8.23 (d, 2H, J=8), 8.79 (t, 1H). [M+1] 565.02 (C27H27F4N3O4S requires 565.58).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure, water
  3. additionwas added to the residue that
  4. extractionis extracted with EtOAc (3×30 mL)
  5. washwashed with brine (1×40 mL)
  6. dry with materialThe separated organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customthe residue was purified by flash chromatography (3/7 EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-f2cfd55aeb1849d29f5f7546b6a647f3
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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