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

HRID 1476216Notes

Reaction equation

HRID 1476216 reaction equation
[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[CH:39]=[CH:38][CH:37]=[C:36](B3OC(C)(C)C(C)(C)O3)[C:35]=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:36]3[CH:37]=[CH:38][CH:39]=[C:40]4[C:35]=3[CH:34]=[N:33][NH:32]4)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 454801864-(4,4,5,5-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

Product 1

HCID 582690912-(1-(4-amino-3-(1H-indazol-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-oneYield 13%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57c (0.350 g, 1.00 mmoles) in DMF (8 ml), ethanol (4 ml) and water (4 ml), 4-Indazoleboronic acid pinacol ester (0.322 g, 1.32 mmoles) and sodium carbonate (0.349 g, 3.3 mmoles) were added and the system is degassed for 30 min Tetrakis triphenylphosphine Palladium (0.150 g, 0.130 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 off-white solid (0.045 g, 13% yield). MP: 231-233° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 13.25(s,1H), 8.10(s,1H), 8.06(m, 2H), 7.86(m,1H), 7.66(t, J=9.0Hz, 2H), 7.54(m, 2H), 7.33(t, J=6.7Hz, 2H), 7.11-7.06(m,3H), 6.07(q, J=7.1Hz, 1H),1.94(d, J=7.0Hz, 3H). Mass: 517.96(M+).

Workup

  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

Sources & evidence

ORD record
ord-a87f30847b2a49ab97b42bb3e0098410
Source dataset
uspto-grants-2015_04
Patent number
US09018375B2

Reaction notes

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