Hydrochloric Acid → HCID 118131428, compound

HRID 634513Notes

Reaction equation

HRID 634513 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][C:20]([F:30])=[CH:19][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.C([O-])([O-])=O.[K+].[K+].Cl>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+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][C:20]([F:30])=[CH:19][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

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 447173083-Fluoro-5-hydroxybenzeneboronic acidHCID 118131279HCID 118131279, compound

Product 1

HCID 118131428HCID 118131428, compoundYield 35.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

In a sealed vial, a mixture of 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-4-phenyl-1H-isochromen-1-one (intermediate D32, 0.240 g, 0.455 mmol), (3-fluoro-5-hydroxyphenyl)boronic acid (0.156 g, 1 mmol) and K2CO3 (0.138 g, 1 mmol) in dioxane/H2O 4:1 (10 ml) was degassed; Pd(dppf)Cl2 (0.04 g, 0.054 mmol) was added and the reaction was heated at 120° C. for 4 hrs. 1M HCl was added (pH≈1) and the mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with brine and dried over sodium sulfate. The solvent was removed and the crude was purified by flash chromatography on Biotage silica gel cartridge (cyclohexane:EtOAc=95:5 to =20:80) and then triturated with ACN to yield title compound as a white solid (0.08 g, 0.16 mmol).

Workup

  1. customwas degassed
  2. customthe mixture was partitioned between EtOAc and water
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customThe solvent was removed
  7. customthe crude was purified by flash chromatography on Biotage silica gel cartridge (cyclohexane:EtOAc=95:5 to =20:80)
  8. customtriturated with ACN

Sources & evidence

ORD record
ord-1add1ba07a6447cda9efea3bc8de6f2d
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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