Diethyl Pyrocarbonate → 1-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide

HRID 1479857Notes

Reaction equation

HRID 1479857 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.[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>[Cl:1][C:2]1[S:6][C:5]([S:7]([N:10]([CH2:17][CH3:18])[C:11]2([C:14]([NH:42][CH2:41][C:39]3[CH:38]=[C:37]([C:43]4[CH:44]=[CH:45][C:46]([C:49]([F:52])([F:50])[F:51])=[CH:47][CH:48]=4)[N:36]=[C:35]([N:30]4[CH2:31][CH2:32][CH2:33][CH2:34]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 66832317[2-Pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamineHCID 903841961-[(5-Chloro-2-thienyl)sulfonyl-ethyl-amino]cyclopropanecarboxylic acid

Product 1

HCID 903842751-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamideYield 38.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of acid 18 (0.24 g, 0.76 mmol) in THF (20 mL) was added with DEPC (0.15 mL, 1.3 mol eq) and the mixture was stirred at room temperature for several minutes. Then [2-pyrrolidin-1-yl-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27A (0.27 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 and washed with water (1×50 mL) and brine. After drying over Na2SO4, the separated organic phase was evaporated under reduced pressure and the residue was purified by flash chromatography (1:1 EtOAc:Petroleum ether) to afford a pale yellow solid (0.18 g) after crystallization from a mixture of ethyl ether/petroleum ether. Yield=38%, 1HNMR (DMSO, 200 MHz) δ 0.86 (t, 3H), 1.21 (m, 4H), 1.91 (m, 4H), 3.42 (m, 6H), 4.21 (d, 2H, J=6.2), 6.26 (s, 1H), 6.45 (s, 1H), 7.27 (d, 1H, J=4), 7.58 (d, 1H, J=3.8), 7.82 (d, 2H, J=7.8), 8.21 (d, 2H, J=8.1), 8.41 (t, 1H); [M+1] 613.11 (C27H28ClF3N4O3S2 requires 612.12).

Workup

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

Sources & evidence

ORD record
ord-6107d2c5287540ac85dec92b0c238608
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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