Hydrochloric Acid → HCID 118131356, compound

HRID 634512Notes

Reaction equation

HRID 634512 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](=[O:31])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:21][CH:20]=[C:19]([CH3:30])[CH:18]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[F:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[C:37]([OH:39])[CH:38]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+].Cl>CN(C=O)C.CCO.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[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](=[O:31])[C:17]4[C:22]([C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:21][CH:20]=[C:19]([CH3:30])[CH:18]=4)[CH3:13])[N:9]=[C:10]([C:35]3[CH:36]=[C:37]([OH:39])[CH:38]=[C:33]([F:32])[CH:34]=3)[C:3]=12

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 118131076HCID 118131076, compound2×

Product 1

HCID 118131356HCID 118131356, compoundYield 24%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

3-(1-(4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-7-methyl-4-phenyl-1H-isochromen-1-one (intermediate D29, 0.100 g, 0.19 mmol), (3-fluoro-5-hydroxyphenyl)boronic acid (0.036 g, 0.229 mmol) and PPh3 (0.030 g, 0.114 mmol) were dissolved in a mixture of DMF (10 ml), EtOH (4 ml) and water (4 ml); Na2CO3 (0.101 g, 0.95 mmol) was added and the mixture was degasses under nitrogen. Pd(OAc)2 (0.009 g, 0.038 mmol) was added and the reaction was heated at 80° C. for 15 min. 1M HCl was added (pH≈2) and the mixture was partitioned between EtOAc and water. The organic phase was extracted with EtOAc and the combined organic layers were washed several times with brine and dried over sodium sulfate. The solvent was removed and the crude was purified by flash chromatography on Biotage silica gel cartridge (DCM to DCM:MeOH=97:3) to afford the title compound (0.023 g, 0.045 mmol, 24%).

Workup

  1. customthe mixture was partitioned between EtOAc and water
  2. extractionThe organic phase was extracted with EtOAc
  3. washthe combined organic layers were washed several times with brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed
  6. customthe crude was purified by flash chromatography on Biotage silica gel cartridge (DCM to DCM:MeOH=97:3)

Sources & evidence

ORD record
ord-621f7bbe2a9148f8a7aa70f0f578bbba
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

Loading…