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

HRID 1476211

반응식

HRID 1476211 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:30])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[NH:31]1[C:39]2[C:34](=[CH:35][CH:36]=[C:37](B3OC(C)(C)C(C)(C)O3)[CH:38]=2)[CH:33]=[N:32]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:30])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:37]3[CH:38]=[C:39]4[C:34]([CH:33]=[N:32][NH:31]4)=[CH:35][CH:36]=3)[C:3]=12

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 441192506-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazoleHCID 582691102-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-phenyl-4H-chromen-4-one

생성물 1

HCID 582691382-(1-(4-amino-3-(1H-indazol-6-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-phenyl-4H-chromen-4-one수율 10.2%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

To a solution of Example 57b (0.500 g, 0.98 mmoles) in DMF (10 ml), ethanol (4 ml) and water (4 ml), 6-Indazoleboronic acid pinacol ester (0.478 g, 1.96 mmoles) and sodium carbonate (0.519 g, 4.90 mmoles) were added and the system is degassed for 30 min Tetrakis triphenylphosphine Palladium (0.214 g, 0.185 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 (0.050 g, 10% yield). MP: 176-178° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 13.18(s,1H), 8.14(s,1H), 8.09(s,1H), 8.05(dd, J=8.0,1.6 Hz,1H),7.91(d, J=8.3Hz, 1H), 7.83(m,1H), 7.73(s, 1H), 7.63(d, J=8.3Hz, 1H), 7.52(dt, J=7.9,0.8 Hz, 1H), 7.41(dd, J=8.3,1.2Hz, 1H), 7.31-7.16(m, 5H), 6.01(q, J=6.9Hz, 1H), 1.92(d, J=7.1Hz, 3H). Mass: 500.04(M++1).

후처리

  1. additionwas added under nitrogen atmosphere
  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-8d63e88f0e4b4af1ab0a68b332d1da8d
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018375B2

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