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

HRID 1484360Notes

Reaction equation

HRID 1484360 reaction equation
[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.C([NH:33][C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1)(=O)C.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:38]3[CH:37]=[CH:36][CH:35]=[C:34]([NH2:33])[CH:39]=3)[C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 157274(3-Acetamidophenyl)boronic acidHCID 582691472-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-one

Product 1

HCID 582693132-((4-amino-3-(3-aminophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-3-phenyl-4H-chromen-4-oneYield 38%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 57a (0.400 g, 0.804 mmoles) in DMF (10 ml), ethanol (5 ml) and water (5 ml), 3-Acetamidophenyl boronic acid (0.187 g, 1.045 mmoles) and sodium carbonate (0.426 g, 4.02 mmoles) were added and the system is degassed for 30 min. Palladium tetrakis triphenylphosphine (0.183 g, 0.158 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. To the concentrate ethanol (5 ml) and Con.HCl (0.5 ml) were added and refluxed for 2 h. The reaction mixture was basified with sodium carbonate solution 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 yellow solid (0.140 g, 38% yield). MP: 157-159° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 8.21 (s, 1H), 8.06 (dd, J=7.8, 1.3 Hz, 1H), 7.77 (dt, J=8.6, 1.5 Hz, 1H), 7.49 (t, J=7.4 Hz, 1H), 7.37-7.29 (m, 5H), 7.17 (t, J=7.7 Hz, 1H), 6.84 (s, 1H), 6.71 (d, J=7.5 Hz, 1H), 6.65 (d, J=7.9 Hz, 1H), 5.51 (s, 2H), 5.34 (s, 2H). Mass: 460.84 (M+).

Workup

  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. additionHCl (0.5 ml) were added
  7. temperaturerefluxed for 2 h
  8. extractionextracted with ethyl acetate
  9. dry with materialThe organic layer was dried over sodium sulphate
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified by column chromatography with methanol

Sources & evidence

ORD record
ord-207ca042ffc24421afb45dd0e64cbefc
Source dataset
uspto-grants-2016_08
Patent number
US09421209B2

Reaction notes

Loading…