8-Hydroxyquinoline → tert-Butyl 7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

HRID 1020670ノート

反応式

HRID 1020670 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][NH:11][C:10](=[O:14])[CH:9]=2)=[C:4]([O:15][CH3:16])[CH:3]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:23]=3[N:24]([CH3:27])[C:25]=2[CH:26]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]([C:18]3[CH:19]=[CH:20][C:21]4[C:22]5[CH2:31][N:30]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:29][CH2:28][C:23]=5[N:24]([CH3:27])[C:25]=4[CH:26]=3)[C:10](=[O:14])[CH:9]=2)=[C:4]([O:15][CH3:16])[CH:3]=1

参加物

7

反応物 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 532180124-(4-Chloro-2-methoxyphenyl)pyridin-2(1H)-oneHCID 57950375tert-Butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate

生成物 1

HCID 57950289tert-Butyl 7-(4-(4-chloro-2-methoxyphenyl)-2-oxopyridin-1(2H)-yl)-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate収率 44.3%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
135 °C

実験手順

A suspension of 4-(4-chloro-2-methoxyphenyl)pyridin-2(1H)-one (126 mg, 0.534 mmol), tert-butyl 7-bromo-5-methyl-3,4-dihydro-1H-pyrido[4,3-b]indole-2(5H)-carboxylate (234 mg, 0.641 mmol), CuI (122 mg, 0.641 mmol), 8-hydroxyquinoline (93 mg, 0.64 mmol) and Cs2CO3 (191 mg, 0.587 mmol) in DMSO (5 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and heated at 135° C. with stirring overnight. The suspension was cooled, 40:9:1 CH2Cl2/MeOH/NH4OH was added, and the resulting suspension was stirred at 25° C. for 10 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. The solution was dried over Na2SO4 and concentrate under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH) 100:0 to 0:100) gave the title compound (123 mg, 44%) as a yellow solid: 1H NMR (300 MHz, CDCl3) δ 7.54 (d, J=8.1 Hz, 1H), 7.42-7.35 (m, 2H), 7.31 (d, J=8.1 Hz, 1H), 7.12-7.02 (m, 2H), 6.99 (d, J=1.8 Hz, 1H), 6.81 (d, J=1.8 Hz, 1H), 6.44 (dd, J=7.2, 1.8 Hz, 1H), 4.65 (br s, 2H), 3.88 (s, 3H), 3.90-3.81 (m, 2H), 3.65 (s, 3H), 2.87-2.79 (m, 2H), 1.51 (s, 9H).

後処理

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition40:9:1 CH2Cl2/MeOH/NH4OH was added
  4. stirringthe resulting suspension was stirred at 25° C. for 10 min
  5. washthe filtrate was washed with brine
  6. dry with materialThe solution was dried over Na2SO4
  7. concentrationconcentrate under reduced pressure

出典と根拠

ORDレコード
ord-68aba7a34e634d87afcc93ad5e6fb901
出典データセット
uspto-grants-2014_05
特許番号
US08716308B2

反応ノート

読み込み中…