三(邻甲基苯基)磷 → (E)-N-Methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-[6-(phenylamino)pyridin-3-yl]acrylamide

HRID 1921069笔记

反应方程式

HRID 1921069 反应方程式
[CH3:1][N:2]([CH2:7][C:8]1[N:9]([CH3:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3](=[O:6])[CH:4]=[CH2:5].[C:18]1([NH:24][C:25]2[CH:30]=[CH:29][C:28](Br)=[CH:27][N:26]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][N:2]([CH2:7][C:8]1[N:9]([CH3:17])[C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:3](=[O:6])/[CH:4]=[CH:5]/[C:28]1[CH:27]=[N:26][C:25]([NH:24][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:30][CH:29]=1

参与物

7

反应物 4

HCID 80271三(邻甲基苯基)磷HCID 81531N,N-二异丙基乙胺HCID 133140415-BROMO-2-PHENYLAMINOPYRIDINEHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamide

产物 1

HCID 60208936(E)-N-Methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-[6-(phenylamino)pyridin-3-yl]acrylamide收率 69%

试剂、催化剂与溶剂 2

HCID 167845乙酸钯(Ⅱ)催化剂HCID 7854丙腈溶剂

实验过程

N-Methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (from Example 76 (a)) was taken up in propionitrile (50 mL). To this solution was added with stirring 2-phenylamino-5-bromopyridine (1.3 g, 5.2 mmole), DIEA (1.8 mL, 10 mmole), Pd(OAc)2 (112 mg, 05 mmole) and P(o-tol)3 (304 mg, 1.0 mmole). The reaction was purged with argon then stirred at reflux for 16 h. After cooling to room temperature the reaction was concentrated to dryness under vacuum. Flash chromatography on silica gel (5% methanol/CHCl3) followed by a second flash column on silica gel (50-70% EtOAc/CHCl3) left a residue that was triturated with EtOAc/petroleum ether. Filtration and drying under vacuum gave the title compound (1.42 g, 69%) as an off-white powder: MS (ES) m/e 396.20 (M+H)+.

后处理

  1. customThe reaction was purged with argon
  2. temperatureat reflux for 16 h
  3. concentrationwas concentrated to dryness under vacuum
  4. waitleft a residue that
  5. customwas triturated with EtOAc/petroleum ether
  6. filtrationFiltration
  7. customdrying under vacuum

来源与证据

ORD记录
ord-1f4b01e755c6415faf7c68986c7bc736
来源数据集
uspto-grants-2012_05
专利号
US08173646B2

反应笔记

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