Diethyl Pyrocarbonate → 1-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide

HRID 1479847Notes

Reaction equation

HRID 1479847 reaction equation
[CH2:1]([N:3]([S:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[C:4]1([C:7]([OH:9])=O)[CH2:6][CH2:5]1)[CH3:2].CCOC(OC(OCC)=O)=O.[F:31][C:32]([F:49])([F:48])[O:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[C:44]([CH2:46][NH2:47])[CH:43]=[CH:42][N:41]=2)=[CH:36][CH:35]=1>C1COCC1>[CH2:1]([N:3]([S:10]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)(=[O:12])=[O:11])[C:4]1([C:7]([NH:47][CH2:46][C:44]2[CH:43]=[CH:42][N:41]=[C:40]([C:37]3[CH:36]=[CH:35][C:34]([O:33][C:32]([F:49])([F:31])[F:48])=[CH:39][CH:38]=3)[CH:45]=2)=[O:9])[CH2:5][CH2:6]1)[CH3:2]

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68759664[2-[4-(Trifluoromethoxy)phenyl]-4-pyridyl]methanamineHCID 903843631-[Ethyl-(4-fluorophenyl)sulfonyl-amino]cyclopropanecarboxylic acid

Product 1

HCID 903841711-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-[4-(trifluoromethoxy)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamideYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 15A (0.5 g, 1.7 mmol) in THF (30 mL) was added with DEPC (0.34 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 (0.51 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, the residue was suspended in EtOAc (40 mL) and washed with water (50 mL) and brine. The separated organic phase was dried over Na2SO4 and evaporated under reduced pressure and the residue was purified by flash chromatography (7:3 EtOAc:Petroleum ether) to afford a white solid (0.18 g) after crystallization from diethyl ether. Yield=30%, 1HNMR (DMSO, 200 MHz) δ 1.09 (bs, 2H), 1.22 (t, 3H, J=8), 1.26 (bs, 2H), 3.41 (bs, 2H), 4.43 (d, 2H, J=6); 7.27 (d, 1H, J=4), 7.46-7.42 (m, 4H), 7.90 (m, 3H), 8.23 (m, 3H), 8.61 (d, 1H, J=5.2). [M+1] 537.53 (C25H23F4N3O4S requires 537.13).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure
  3. washwashed with water (50 mL) and brine
  4. dry with materialThe separated organic phase was dried over Na2SO4
  5. customevaporated under reduced pressure
  6. customthe residue was purified by flash chromatography (7:3 EtOAc:Petroleum ether)

Sources & evidence

ORD record
ord-9a799c790f9f46ea9dd340b2f46a91c2
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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