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 2112722ノート

反応式

HRID 2112722 の反応式
[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

参加物

7

反応物 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

生成物 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)acrylamide収率 59.1%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 7854Propionitrile溶媒

実験手順

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)+.

後処理

  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), trituration
  6. filtrationwith ethyl acetate, filtration
  7. customdrying under vacuum

出典と根拠

ORDレコード
ord-6ba1c61cc23849fcbd3af3b8d7f2b8f4
出典データセット
uspto-grants-2009_04
特許番号
US07524843B2

反応ノート

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