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

HRID 239654노트

반응식

HRID 239654 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[O:14][C:15]4[C:20]([C:21](=[O:29])[C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:9]=[C:10](I)[C:3]=12.[NH:30]1[C:38]2[CH:37]=[CH:36][CH:35]=[C:34](B3OC(C)(C)C(C)(C)O3)[C:33]=2[CH:32]=[N:31]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]([CH2:12][C:13]3[O:14][C:15]4[C:20]([C:21](=[O:29])[C:22]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:9]=[C:10]([C:34]3[CH:35]=[CH:36][CH:37]=[C:38]4[C:33]=3[CH:32]=[N:31][NH:30]4)[C:3]=12

참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 454801864-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazoleHCID 582691472-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-one

생성물 1

HCID 582691572-((4-amino-3-(1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-one수율 8.2%

시약·촉매·용매 3

HCID 702Ethanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

To a solution of Example 57a (0.500 g, 1.00 mmoles) in DMF (5 ml), ethanol (2.5 ml) and water (2.5 ml), 4-Indazoleboronic acid pinacol ester (0.491 g, 2.00 mmoles) and sodium carbonate (0.533 g, 5.02 mmoles) were added and the system is degassed for 30 min. Tetrakis triphenylphosphine Palladium (0.229 g, 0.197 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 (0.040 g, 8% yield). MP: 248-252° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 13.24(s,1H), 8.27(s,1H), 8.07(dd, J=7.9, 1.6 Hz, 1H),8.01(s, 1H), 7.78(m,1H), 7.63(d, J=8.4 Hz, 1H), 7.51-7.32(m, 10H), 7.14(br s,1H),5.56(s, 1H). Mass: 486.04(M++1).

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-817da8da175147c49c9bcceed1ebd3a3
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08642607B2

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