Tri-o-tolylphosphine → (E)-N-Methyl-N-(1-methyl-1H-indol-2-ylmethyl)-3-[6-(phenylamino)pyridin-3-yl]acrylamide

HRID 225943노트

반응식

HRID 225943 반응식
[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

참가 물질

7

반응물 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 133140415-bromo-N-phenylpyridin-2-amineHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamide

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 7854Propionitrile용매

실험 절차

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, 0.5 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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-c897d192d75d4e1e942d73071bb3f0c3
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557125B2

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