Diethyl Pyrocarbonate → 1-[(4-fluorophenyl)sulfonylamino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide

HRID 1479855Notes

Reaction equation

HRID 1479855 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2([C:15]([OH:17])=O)[CH2:14][CH2:13]2)(=[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>[F:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C:12]2([C:15]([NH:41][CH2:40][C:38]3[CH:37]=[C:36]([C:42]4[CH:43]=[CH:44][C:45]([C:48]([F:51])([F:49])[F:50])=[CH:46][CH:47]=4)[N:35]=[C:34]([N:29]4[CH2:30][CH2:31][CH2:32][CH2:33]4)[CH:39]=3)=[O:17])[CH2:13][CH2:14]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 607292541-[(4-Fluorophenyl)sulfonylamino]cyclopropanecarboxylic acidHCID 66832317[2-Pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine

Product 1

HCID 903842311-[(4-fluorophenyl)sulfonylamino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamideYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 15C (0.50 g, 1.75 mmol) in THF (25 mL) was added with DEPC (0.34 mL, 1.3 mol eq) and the mixture was stirred at room temperature for 5′. Then [2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27A (0.61 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 (40 mL) 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 pale orange solid (0.21 g) after crystallization from a mixture of ethyl ether/petroleum ether. Yield=22%, 1HNMR (DMSO, 200 MHz) δ 0.71 (m, 2H), 1.09 (m, 2H9, 1.96 (m, 4H), 3.38 (m, 4H), 4.18 (d, 2H, J=6.1), 6.33 (s, 1H), 6.46 (s, 1H), 7.47-7.38 (m, 4H), 7.88-7.80 (m, 4H), 8.37 (t, 1H), 8.71 (bs, 1H); [M+1] 562.58 (C27H26F4N4O3S requires 562.16).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure, water (40 mL)
  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-d7604932fb624b27be8a9841e3ea914d
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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