Diethyl Pyrocarbonate → 1-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[3-[4-(trifluoromethoxy)phenyl]phenyl]methyl]cyclopropanecarboxamide

HRID 1479878Notes

Reaction equation

HRID 1479878 reaction equation
[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([CH2:17][CH3:18])[C:11]2([C:14]([OH:16])=O)[CH2:13][CH2:12]2)(=[O:9])=[O:8])=[CH:4][CH:3]=1.CCOC(OC(OCC)=O)=O.[F:30][C:31]([F:48])([F:47])[O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:40]=[C:41]([CH2:45][NH2:46])[CH:42]=[CH:43][CH:44]=2)=[CH:35][CH:34]=1>C1COCC1>[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([CH2:17][CH3:18])[C:11]2([C:14]([NH:46][CH2:45][C:41]3[CH:42]=[CH:43][CH:44]=[C:39]([C:36]4[CH:37]=[CH:38][C:33]([O:32][C:31]([F:30])([F:47])[F:48])=[CH:34][CH:35]=4)[CH:40]=3)=[O:16])[CH2:12][CH2:13]2)(=[O:8])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 61032752(4'-(Trifluoromethoxy)-[1,1'-biphenyl]-3-yl)methanamineHCID 903841961-[(5-Chloro-2-thienyl)sulfonyl-ethyl-amino]cyclopropanecarboxylic acid

Product 1

HCID 903903051-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[3-[4-(trifluoromethoxy)phenyl]phenyl]methyl]cyclopropanecarboxamideYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 18 (0.20 g, 0.65 mmol) in THF (15 mL) was added with DEPC (0.13 mL, 1.3 mol eq) and the mixture was stirred at room temperature for 10 minutes. Then [3-[4-(trifluoromethoxy)phenyl]phenyl]methanamine 23B (0.19 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 (45 mL) and washed with water (40 mL) and brine. The separated organic phase was dried over an. Na2SO4 and evaporated under reduced pressure. The residue was purified by flash chromatography (1/1 EtOAc/Petroleum ether) to afford a white solid (0.2 g). Yield=59%, 1HNMR (DMSO, 200 MHz) δ 1.23 (m, 5H), 1.41 (m, 2H), 3.36 (m, 2H), 4.39 (d, 2H, J=6.1), 7.25 (m, 2H), 7.45 (m, 4H), 7.57 (m, 2H), 7.79 (d, 2H, J=7.9), 8.09 (t, 1H). [M+1] 559.31 (C24H22ClF3N2O4S2 requires 559.02).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. washwashed with water (40 mL) and brine
  4. customThe separated organic phase was dried over an
  5. customNa2SO4 and evaporated under reduced pressure
  6. customThe residue was purified by flash chromatography (1/1 EtOAc/Petroleum ether)

Sources & evidence

ORD record
ord-5ee2c3d49e1d45098cef8928e9750926
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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