Diethyl Pyrocarbonate → 2-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamide

HRID 1479874

反応式

HRID 1479874 の反応式
[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([OH:7])=O)[CH3:2].CCOC(OC(OCC)=O)=O.[O:30]1[CH2:35][CH2:34][N:33]([C:36]2[CH:41]=[C:40]([CH2:42][NH2:43])[CH:39]=[C:38]([C:44]3[CH:49]=[CH:48][C:47]([C:50]([F:53])([F:52])[F:51])=[CH:46][CH:45]=3)[N:37]=2)[CH2:32][CH2:31]1>C1COCC1>[CH2:1]([N:3]([S:9]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[C:4](=[CH2:8])[C:5]([NH:43][CH2:42][C:40]1[CH:39]=[C:38]([C:44]2[CH:45]=[CH:46][C:47]([C:50]([F:53])([F:51])[F:52])=[CH:48][CH:49]=2)[N:37]=[C:36]([N:33]2[CH2:34][CH2:35][O:30][CH2:31][CH2:32]2)[CH:41]=1)=[O:7])[CH3:2]

参加物

5

反応物 3

HCID 3051Diethyl PyrocarbonateHCID 903842012-[Ethyl-(4-fluorophenyl)sulfonyl-amino]prop-2-enoic acidHCID 90390699[2-Morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine

生成物 1

HCID 903902312-[ethyl-(4-fluorophenyl)sulfonyl-amino]-N-[[2-morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methyl]prop-2-enamide収率 12%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of acid 4B (0.40 g, 1.46 mmol) in THF (20 mL) was added with DEPC (0.28 mL, 1.3 mol eq) and the mixture was stirred at room temperature several minutes. Then [2-morpholino-6-[4-(trifluoromethyl)phenyl]-4-pyridyl]methanamine 27B (530 mg, 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 (1×40 mL). The separated organic phase was dried over Na2SO4, evaporated to dryness and the residue was purified by flash chromatography (6/4 EtOAc/Petroleum ether) to afford a white solid (95 mg) after crystallization from ethyl ether. Yield=12%. 1HNMR (DMSO, 200 MHz) δ 1.087 (t, 3H, J=7.8), 3.39 (q, 2H, J=7.6), 3.55 (m, 4H), 3.71 (m, 4H), 4.42 (d, 2H, J=6.2), 5.13 (s, 1H), 6.12 (s, 1H), 6.85 (s, 1H), 7.35 (s, 1H), 7.47 (t, 2H, J=8), 7.83-7.90 (m, 4H), 8.26 (d, 2H, J=8), 8.80 (bt, 1H). [M+1] 592.33 (C28H28F4N4O4S requires 592.60).

後処理

  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 (1×40 mL)
  6. dry with materialThe separated organic phase was dried over Na2SO4
  7. customevaporated to dryness
  8. customthe residue was purified by flash chromatography (6/4 EtOAc/Petroleum ether)

出典と根拠

ORDレコード
ord-e4708b418ba5452d9d9d754b0fab0fe0
出典データセット
uspto-grants-2016_08
特許番号
US09409864B2

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