Potassium Carbonate → 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one

Participants

Role	Name	HCID	Charge
Reactant	Potassium Carbonate	HCID 11430	—
Reactant	3-Fluoro-5-hydroxybenzeneboronic acid	HCID 44717308	—
Reactant	3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one	HCID 118131423	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Dichloromethane	HCID 6344	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one	HCID 118131168	73.7%

Reaction Steps

3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)phenyl)-1H-isochromen-1-one (Intermediate D8, 1.14 g, 1.788 mmol), (3-fluoro-5-hydroxyphenyl)boronic acid (0.558 g, 3.58 mmol), K2CO3 (0.494 g, 3.58 mmol) and PdCl2(dppf) (0.196 g, 0.268 mmol) were reacted in dioxane (30 ml) overnight at 120° C. The reaction was diluted with DCM (100 ml), filtered to remove solids, and the filtrate evaporated under reduced pressure. The crude was purified via flash chromatography on silica gel using a Biotage 100G SNAP with a gradient of DCM and MeOH to give the title compound (819 mg, 73.7%) as brown pale solid.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09321776B2
Source dataset	uspto-grants-2016_04
ORD ID	ord-f1c3c692e24349eb9f5eef13c9fe9e47
Source note	uspto-grants-2016_04