Potassium Iodide → 1-[1-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 1499832ノート

反応式

HRID 1499832 の反応式
[Br:1][C:2]1[C:3]([CH3:14])=[C:4]([Cl:13])[CH:5]=[C:6]([CH:10](Cl)[CH3:11])[C:7]=1[O:8][CH3:9].[CH3:15][C:16]1[C:24]2[C:19](=[N:20][CH:21]=[N:22][C:23]=2[NH2:25])[NH:18][N:17]=1.[I-].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(Cl)Cl>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[C:6]([CH:10]([N:18]2[C:19]3=[N:20][CH:21]=[N:22][C:23]([NH2:25])=[C:24]3[C:16]([CH3:15])=[N:17]2)[CH3:11])[CH:5]=[C:4]([Cl:13])[C:3]=1[CH3:14]

参加物

7

反応物 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 866776443-Bromo-1-chloro-5-(1-chloroethyl)-4-methoxy-2-methylbenzeneHCID 178434474HCID 178434474、化合物

生成物 1

HCID 866776451-[1-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine収率 50%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
140 °C

実験手順

A mixture of 3-bromo-1-chloro-5-(1-chloroethyl)-4-methoxy-2-methylbenzene (150 mg, 0.503 mmol), 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (110 mg, 0.76 mmol, ACES Pharma Product List, item #47024), potassium iodide (9.0 mg, 0.05 mmol) and cesium carbonate (330 mg, 1.0 mmol) in N,N-dimethylformamide (4 mL) and was stirred at 140° C. for 1 h. The mixture was diluted with methylene chloride, washed with sat. NaHCO3, water, brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with 0 to 70% EtOAc in CH2Cl2, to give the desired product (103 mg, 50%). LCMS calculated for C16H18BrClN5O (M+H)+: m/z=410.0; Found: 410.2. The racemic products were applied on a Phenomenex Lux-Cellulose 1 column (21.1×250 mm, 5 micron particle size), eluting with 5% ethanol in hexanes at a flow rate of 18 mL/min, ˜13 mg/injection, to provide two enantiomers. Peak 1, retention time: 12.35 min; Peak 2, retention time: 14.98 min,

後処理

  1. washwashed with sat. NaHCO3, water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with 0 to 70% EtOAc in CH2Cl2

出典と根拠

ORDレコード
ord-4d6e62dee28b4eac9217c1fe257cb523
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

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