8-Hydroxyquinoline → tert-Butyl 6-methyl-8-(2-oxo-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-1 (2H)-yl)-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

HRID 474892

反応式

HRID 474892 の反応式
[F:1][C:2]([F:17])([F:16])[C:3]1[N:8]=[N:7][C:6]([C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=2)=[CH:5][CH:4]=1.Br[C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29][C:24]=3[N:25]([CH3:28])[C:26]=2[CH:27]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[CH3:28][N:25]1[C:26]2[CH:27]=[C:19]([N:12]3[CH:13]=[CH:14][C:9]([C:6]4[N:7]=[N:8][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:4][CH:5]=4)=[CH:10][C:11]3=[O:15])[CH:20]=[CH:21][C:22]=2[C:23]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29][C:24]1=2

参加物

7

反応物 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 579502624-(6-(Trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-oneHCID 58093439tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

生成物 1

HCID 66873862tert-Butyl 6-methyl-8-(2-oxo-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-1 (2H)-yl)-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate収率 31.3%

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-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-one (106 mg, 0.438 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (183 mg, 0.482 mmol), CuI (100 mg, 0.526 mmol), 8-hydroxyquinoline (13 mg, 0.09 mmol) and Cs2CO3 (157 mg, 0.482 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under Ar and stirred at 135° C. overnight. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded the title compound (74 mg, 30%) as a viscous oil: 1H NMR (300 MHz, CDCl3) δ 8.10 (d, J=8.7 Hz, 1H), 7.97 (d, J=8.7 Hz, 1H), 7.65 (d, J=6.9 Hz, 1H), 7.62-7.53 (m, 1H), 7.33 (br s, 1H), 7.30-7.21 (overlapping with solvent peak, 2H), 7.08 (d, J=8.1 Hz, 1H), 3.71-3.62 (m, 7H), 3.11-2.98 (m, 4H), 1.49 (s, 9H).

後処理

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added
  4. stirringthe resulting suspension was stirred at 25° C. for 30 min
  5. washthe filtrate was washed with brine
  6. dry with materialThe resulting solution was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-dc14e45cce6d4c1893900be22c19f517
出典データセット
uspto-grants-2014_01
特許番号
US08637501B2

関連ノート

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