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

HRID 1479879
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HRID 1479879 반응식
[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.[CH3:30][O:31][C:32]1[CH:37]=[C:36]([CH2:38][NH2:39])[CH:35]=[C:34]([C:40]2[CH:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][CH:41]=2)[N: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:39][CH2:38][C:36]3[CH:35]=[C:34]([C:40]4[CH:41]=[CH:42][C:43]([C:46]([F:47])([F:48])[F:49])=[CH:44][CH:45]=4)[N:33]=[C:32]([O:31][CH3:30])[CH:37]=3)=[O:16])[CH2:12][CH2:13]2)(=[O:8])=[O:9])=[CH:4][CH:3]=1
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참가 물질

5

반응물 3

HCID 3051Diethyl PyrocarbonateHCID 903841961-[(5-Chloro-2-thienyl)sulfonyl-ethyl-amino]cyclopropanecarboxylic acidHCID 90390870[2-Methoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine

생성물 1

HCID 903902871-[(5-chloro-2-thienyl)sulfonyl-ethyl-amino]-N-[[2-methoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]cyclopropanecarboxamide수율 26%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

A solution of acid 18 (0.3 g, 0.97 mmol) in THF (15 mL) was added with DEPC (0.19 mL, 1.3 mol eq) and the mixture was stirred at room temperature several minutes. Then [2-methoxy-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27I (0.22 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 was added to the residue that is extracted with EtOAc (3×30 mL) and washed with brine (1×30 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 white solid (110 mg) after crystallization from ethyl ether. Yield=26%. 1HNMR (DMSO, 400 MHz) δ 1.21 (t, 5H, J=6.2), 1.41 (m, 2H), 3.54 (m, 2H), 3.94 (s, 3H), 4.18 (bs, 2H), 6.70 (s, 1H), 7.25 (d, 1H, J=2.1), 7.57 (d, 2H, J=2.3), 7.84 (d, 2H, J=8), 8.27 (m, 3H). [M+1] 574.66 (C24H23ClF3N3O4S2 requires 574.04).

후처리

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was removed under reduced pressure, water
  3. additionwas added to the residue that
  4. extractionis extracted with EtOAc (3×30 mL)
  5. washwashed with brine (1×30 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)

출처 및 근거

ORD 기록
ord-9a21d0cf762042e3b00bd2e929f1a6d0
출처 데이터셋
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09409864B2

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