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

HRID 1479877Notes

Reaction equation

HRID 1479877 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:47])([F:46])[C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[C:42]([CH2:44][NH2:45])[CH:41]=[CH:40][N:39]=2)=[CH:34][CH:33]=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:45][CH2:44][C:42]3[CH:41]=[CH:40][N:39]=[C:38]([C:35]4[CH:36]=[CH:37][C:32]([C:31]([F:47])([F:30])[F:46])=[CH:33][CH:34]=4)[CH:43]=3)=[O:16])[CH2:12][CH2:13]2)(=[O:8])=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 3051Diethyl PyrocarbonateHCID 68758847[2-(4-Trifluoromethyl-phenyl)-pyridin-4-yl]methylamineHCID 903841961-[(5-Chloro-2-thienyl)sulfonyl-ethyl-amino]cyclopropanecarboxylic acid

Product 1

HCID 903903111-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamideYield 18%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Acid 18 (0.3 g, 1.09 mmol) was dissolved in 15 ml of THF and at rt DEPC (1.3 equiv, 0.21 mL) and [2-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 21A (1.1 mol equiv., 0.37 g) were added to the solution. The mixture was stirred at rt overnight then evaporated. The residue was dissolved in AcOEt (30 mL) and washed with water (1×20 mL) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude by chromatographic column (EtOAc 3/petroleum ether 7) afforded 100 mg of a white solid. Yield=18% 1HNMR (DMSO, 200 MHz) δ 1.24 (m, 5H), 1.35 (m, 2H), 3.45 (m, 2H), 4.44 (d, 2H, J=6.2), 7.26 (m, 3H), 6.61 (d, 1H, J=2.1), 7.88 (d, 2H, J=7.8), 7.94 (s, 1H), 8.31 (d, 3H, J=8), 8.64 (d, 1H, J=4.1). [M+1] 543.95 (C23H21ClF3N3O3S2 requires 544.01).

Workup

  1. additionwere added to the solution
  2. customthen evaporated
  3. dissolutionThe residue was dissolved in AcOEt (30 mL)
  4. washwashed with water (1×20 mL) and brine
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe purification of the crude by chromatographic column (EtOAc 3/petroleum ether 7)

Sources & evidence

ORD record
ord-440645edcd76449fbc6975279a97a03a
Source dataset
uspto-grants-2016_08
Patent number
US09409864B2

Reaction notes

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