Methane → tert-Butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H) carboxylate

HRID 474948

反応式

HRID 474948 の反応式
[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][NH:11][C:10](=[O:14])[CH:9]=2)=[CH:4][CH:3]=1.Br[C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[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+].C>CS(C)=O.C(Cl)Cl.[Cu]I>[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:18]3[CH:19]=[CH:20][C:21]4[C:22]5[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28][C:23]=5[N:24]([CH3:27])[C:25]=4[CH:26]=3)[C:10](=[O:14])[CH:9]=2)=[CH:4][CH:3]=1

参加物

9

反応物 5

HCID 297MethaneHCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 220499004-(4-Fluorobenzyloxy)-1h-pyridin-2-oneHCID 58093439tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

生成物 1

HCID 58093437tert-Butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H) carboxylate収率 64.4%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

A suspension of 4-(4-fluorobenzyloxy)pyridin-2(1H)-one (79 mg, 0.36 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (150 mg, 0.40 mmol), 8-hydroxyquinoline (11 mg, 0.072 mmol) and Cs2CO3 (129 mg, 0.40 mmol) in DMSO (10 mL) was degassed under reduced pressure for 40 min. CuI (82 mg, 0.43 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 2×5 min. 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 5 min. Celite was added, and the suspension was stirred for 5 min. The suspension was filtered through Celite, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Purification by preparative TLC (DCM/MeOH/concentrated ammonia 98:1.8:0.2) gave partially purified product, which was dissolved in DCM and stirred with charcoal for 10 min. The suspension was filtered, and the filtrate was concentrated under reduced pressure to afford the title compound (0.12 g, 64%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.52 (t, J=8.0 Hz, 1H), 7.41 (dd, J=8.5, 5.5 Hz, 2H), 7.31 (d, J=7.5 Hz, 1H), 7.24 (s, 1H), 7.10 (t, J=8.5 Hz, 2H), 7.00 (d, J=8.5 Hz, 1H), 6.07 (s, 1H), 6.02 (dd, J=7.5, 2.0 Hz, 1H), 5.01 (s, 2H), 3.78-3.63 (m, 4H), 3.64 (s, 3H), 3.05-2.98 (m, 4H), 1.50-1.48 (m, 9H).

後処理

  1. customwas degassed under reduced pressure for 40 min
  2. customthe reaction mixture was degassed under reduced pressure for 2×5 min
  3. temperatureThe suspension was cooled
  4. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added
  5. additionCelite was added
  6. stirringthe suspension was stirred for 5 min
  7. filtrationThe suspension was filtered through Celite
  8. washthe filtrate was washed with brine
  9. dry with materialThe resulting solution was dried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customPurification by preparative TLC (DCM/MeOH/concentrated ammonia 98:1.8:0.2)
  12. customgave partially purified product, which
  13. filtrationThe suspension was filtered
  14. concentrationthe filtrate was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-18a1ba6971e6404fb21f6f15622c92c8
出典データセット
uspto-grants-2014_01
特許番号
US08637501B2

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