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

반응식

HRID 239668 반응식
[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

참가 물질

8

반응물 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

생성물 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-one수율 20.4%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-eaee43c982b94f428074dfee9324d9e1
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642607B2

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