Dichloromethane → 2-(1-(4-amino-3-(1H-indazol-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

HRID 239668

反応式

HRID 239668 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[NH:32]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38](B3OC(C)(C)C(C)(C)O3)[CH:39]=2)[CH:34]=[N:33]1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>CN(C=O)C.C(O)C.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:31])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:38]3[CH:39]=[C:40]4[C:35]([CH:34]=[N:33][NH:32]4)=[CH:36][CH:37]=3)[C:3]=12

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 441192506-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazoleHCID 665799322-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

生成物 1

HCID 532348372-(1-(4-amino-3-(1H-indazol-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one収率 20.4%

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

To a solution of Example 57c (0.500 g, 0.758 mmoles) in DMF (4.5 ml), ethanol (2.3 ml) and water (2.3 ml), Indazole-6-boronic acid pinacol ester (0.462 g, 1.89 mmoles) and sodium carbonate (0.502 g, 4.74 mmoles) were added and the system is degassed for 30 min. Tetrakistriphenylphosphine Palladium (0.215 g, 0.186 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol: dichloromethane to afford the title compound as brown solid (0.080 g, 16% yield). MP: 206-208° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 13.19(s,1H), 8.14(s,1H), 8.08(s,1H),8.05(dd, J=7.9,1.5 Hz, 1H), 7.90(d, J=8.3 Hz, 1H), 7.86(m,1H), 7.71(s,1H), 7.69(d, J=8.4 Hz, 1H), 7.53(t, J=7.1 Hz, 1H), 7.39(dd, J=8.2,1.1 Hz, 1H), 7.30(m,2H), 7.07(dt, J=8.7,2.6 Hz, 1H), 6.92(br m, 2H), 6.06(q, J=7.1 Hz, 1H), 1.91(d, J=7.0 Hz, 3H). Mass: 517.96(M+).

後処理

  1. customthe system is degassed for 30 min
  2. concentrationconcentrated
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography with methanol

出典と根拠

ORDレコード
ord-eaee43c982b94f428074dfee9324d9e1
出典データセット
uspto-grants-2014_02
特許番号
US08642607B2

関連ノート

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