Hydrochloric Acid → 4-(Benzyloxy)-1-(2,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride

HRID 1020552ノート

反応式

HRID 1020552 の反応式
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][C:7]=3[N:8]2[CH3:11])=[CH:4][CH:3]=1.[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][NH:28][C:27](=[O:31])[CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+].[ClH:49].CCOCC>CS(C)=O.C(Cl)Cl.[Cu]I>[ClH:49].[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][N:28]([C:2]2[CH:10]=[C:9]3[C:5]([C:6]4[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][C:7]=4[N:8]3[CH3:11])=[CH:4][CH:3]=2)[C:27](=[O:31])[CH:26]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

参加物

10

反応物 6

HCID 313Hydrochloric AcidHCID 19238-HydroxyquinolineHCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 579503597-Bromo-2,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

生成物 1

HCID 686575684-(Benzyloxy)-1-(2,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-7-yl)pyridin-2(1H)-one hydrochloride収率 33%

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
130 °C

実験手順

A stirred solution of 7-bromo-2,9-dimethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (250 mg, 0.895 mmol) in DMSO (4 mL) under nitrogen was treated sequentially with 4-(benzyloxy)pyridin-2(1H)-one (180 mg, 0.895 mmol), 8-hydroxyquinoline (20 mg, 0.14 mmol), CuI (196 mg, 1.04 mmol) and K2CO3 (142 mg, 1.04 mmol). The mixture was placed under vacuum for 30 minutes and then flushed with nitrogen. After stirring overnight at 130° C., the mixture was allowed to cool to room temperature, diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated. Purification by flash column chromatography (12 g ISCO column eluting with methylene chloride and a methanol/ammonia mixture (10:1); gradient 100% methylene chloride to 80% methylene chloride over 30 min at 25 mL/min) provided the free-base. This was dissolved in methylene chloride (2 mL) and treated with 2 N HCl in Et2O (1 equivalent) and the mixture was concentrated to provide the title compound (131 mg, 33%) as a yellow solid: mp 270-274° C.; 1H NMR (500 MHz, CD3OD) δ 7.67-7.63 (m, 2H), 7.50-7.40 (m, 3H), 7.43-7.35 (m, 3H), 7.08 (dd, J=8.3, 1.6 Hz, 1H), 6.40 (dd, J=7.5, 2.6 Hz, 1H), 6.21 (d, J=2.6 Hz, 1H), 5.22 (s, 2H), 4.81-4.80 (m, 1H), 4.58 (d, J=15.3 Hz, 1H), 3.88-3.84 (m, 1H), 3.72 (s, 3H), 3.55-3.49 (m, 1H), 3.21-3.16 (m, 5H); ESI MS m/z 400 [M+H]+; HPLC (Method B)>98.9% (AUC), tR=13.0 min.

後処理

  1. customflushed with nitrogen
  2. temperatureto cool to room temperature
  3. additiondiluted with CH2Cl2
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by flash column chromatography (12 g ISCO column
  8. washeluting with methylene chloride
  9. customgradient 100% methylene chloride to 80% methylene chloride over 30 min at 25 mL/min) provided the free-base
  10. concentrationthe mixture was concentrated

出典と根拠

ORDレコード
ord-1bf865ae48f445bf8785aae744a845c7
出典データセット
uspto-grants-2014_05
特許番号
US08716308B2

反応ノート

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