Diethyl Pyrocarbonate → 2-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamide

HRID 1479867

Reaction equation

HRID 1479867 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.[N:30]1([C:35]2[CH:40]=[C:39]([CH2:41][NH2:42])[CH:38]=[C:37]([C:43]3[CH:48]=[CH:47][C:46]([C:49]([F:52])([F:51])[F:50])=[CH:45][CH:44]=3)[N:36]=2)[CH2:34][CH2:33][CH2:32][CH2:31]1>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:42][CH2:41][C:39]1[CH:38]=[C:37]([C:43]2[CH:44]=[CH:45][C:46]([C:49]([F:52])([F:50])[F:51])=[CH:47][CH:48]=2)[N:36]=[C:35]([N:30]2[CH2:31][CH2:32][CH2:33][CH2:34]2)[CH:40]=1)=[O:7])[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 66832317HCID 66832317, compoundHCID 903842012-[Ethyl-(4-fluorophenyl)sulfonyl-amino]prop-2-enoic acid

Product 1

HCID 903902852-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4B (0.15 g, 0.53 mmol) in THF (10 mL) was added with DEPC (0.10 mL, 1.3 mol eq) and the mixture was stirred at room temperature several minutes. Then [2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27A (0.17 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, water was added to the residue that is extracted with EtOAc (3×25 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 (1/1 EtOAc/Petroleum ether) to afford a white solid (90 mg) after crystallization from ethyl ether. Yield=32%. 1HNMR (DMSO, 200 MHz) δ 1.092 (t, 3H, J=5.6), 1.95 (m, 4H), 3.4-3.46 (m, 6H), 4.39 (d, 2H, J=6), 5.13 (s, 1H), 6.12 (s, 1H), 6.47 (s, 1H), 7.20 (s, 1H), 7.51 (t, 2H, J=7.9), 7.80-7.90 (m, 4H), 8.27 (d, 2H, J=8.1), 8.78 (bt, 1H). [M+1] 576.28 (C28H28F4N4O3S requires 576.60).

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 (3×25 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 (1/1 EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-ca065649a1aa4d88a4ff72f2ac8be91f
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Linked notes

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