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

HRID 1479825Notes

Reaction equation

HRID 1479825 reaction equation
[Cl: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.[N:29]1([C:34]2[CH:39]=[C:38]([CH2:40][NH2:41])[CH:37]=[C:36]([C:42]3[CH:47]=[CH:46][C:45]([C:48]([F:51])([F:50])[F:49])=[CH:44][CH:43]=3)[N:35]=2)[CH2:33][CH2:32][CH2:31][CH2:30]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([N:11]([CH3:17])[C:12](=[CH2:16])[C:13]([NH:41][CH2:40][C:38]2[CH:37]=[C:36]([C:42]3[CH:43]=[CH:44][C:45]([C:48]([F:51])([F:49])[F:50])=[CH:46][CH:47]=3)[N:35]=[C:34]([N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[CH:39]=2)=[O:15])(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 66832317[2-Pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamineHCID 1317365842-[(4-Chlorophenyl)sulfonyl-methyl-amino]prop-2-enoic acid

Product 1

HCID 783205252-[(4-chlorophenyl)sulfonyl-methyl-amino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamideYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 4C (0.40 g, 1.45 mmol) in THF (20 mL) was added with DEPC (0.28 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 (0.51 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 (0.18 g) after crystallization from ethyl ether. Yield=22%, 1HNMR (DMSO, 200 MHz) δ 1.95 (m, 4H), 2.95 (s, 3H), 3.46 (m, 4H), 4.36 (d, 2H), 5.12 (s, 1H), 5.86 (s, 1H), 6.52 (s, 1H), 7.22 (s, 1H), 7.73 (d, 2H, JO 7.9), 7.82-7.79 (m, 5H), 8.26 (d, 2H, J=7.8), 8.85 (t, 1H); [M+1] 579.03 (C27H26ClF3N4O3S requires 578.13).

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-057878a9ddf54aad9e9e560d2baab0d0
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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