Tri-o-tolylphosphine → (E)-N-(1,3-Dimethyl-1H-indol-2-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro[1,8]naphthyridin-3-yl)acrylamide

HRID 225939노트

반응식

HRID 225939 반응식
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:11])=[C:3]1[CH2:12][N:13]([CH3:18])[C:14](=[O:17])[CH:15]=[CH2:16].Br[C:20]1[CH:21]=[C:22]2[C:27](=[N:28][CH:29]=1)[NH:26][C:25](=[O:30])[CH2:24][CH2:23]2.CCN(C(C)C)C(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH3:11])=[C:3]1[CH2:12][N:13]([CH3:18])[C:14](=[O:17])/[CH:15]=[CH:16]/[C:20]1[CH:29]=[N:28][C:27]2[NH:26][C:25](=[O:30])[CH2:24][CH2:23][C:22]=2[CH:21]=1

참가 물질

7

반응물 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 110963256-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-oneHCID 22593810N-(1,3-Dimethyl-1H-indol-2-ylmethyl)-N-methylacrylamide

생성물 1

HCID 23658030(E)-N-(1,3-Dimethyl-1H-indol-2-ylmethyl)-N-methyl-3-(7-oxo-5,6,7,8-tetrahydro[1,8]naphthyridin-3-yl)acrylamide수율 59.1%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 7854Propionitrile용매

실험 절차

To a stirred solution of N-(1,3-dimethyl-1H-indol-2-ylmethyl)-N-methylacrylamide (1.7 g, 7 mmole) in propionitrile (50 mL) was added 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (1.16 g, 5.1 mmole), DIEA (1.8 mL, 10.3 mmole), palladium(II) acetate (112 mg, 0.5 mmole), and tri-o-tolylphosphine (304 mg, 1.0 mmole). The reaction was purged with argon and heated at reflux for 16 hr, then was cooled to RT and concentrated under vacuum. Purification by flash chromatography on silica gel (5% methanol/CHCl3). trituration with ethyl acetate, filtration, and drying under vacuum gave the title compound (1.17 g, 59%) as an off-white solid: LCMS (ES) m/e 389.2 (M+H)+.

후처리

  1. customThe reaction was purged with argon
  2. temperatureheated
  3. temperatureat reflux for 16 hr
  4. concentrationconcentrated under vacuum
  5. customPurification by flash chromatography on silica gel (5% methanol/CHCl3)
  6. filtrationtrituration with ethyl acetate, filtration
  7. customdrying under vacuum

출처 및 근거

ORD 기록
ord-b41835c62a754efa8262b61061831360
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557125B2

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