Cesium fluoride → 4-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol

Participants

Role	Name	HCID	Charge
Reactant	Cesium fluoride	HCID 25953	—
Reactant	(3-Fluoro-4-hydroxyphenyl)boronic acid	HCID 23005361	—
Reactant	3-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine	HCID 68157974	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Product	4-(4-amino-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-fluorophenol	HCID 136166130	34.6%

Reaction Steps

A mixture of 3-iodo-1-((1-phenyl-1H-benzo[d]imidazol-2-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 141 (1.5 g, 3.2 mmol), 3-fluoro-4-hydroxyphenylboronic acid (0.6 g, 3.8 mmol), Pd(dppf)Cl2 (0.3 g) and CsF (1.0 g, 6.4 mmol) in DME (30 mL) and H2O (3 mL) was refluxed overnight. Then the mixture was cooled to room temperature, added H2O (50 mL) and extracted with EtOAc (30 mL×3). The combined organic layers were washed with brine and concentrated in vacuo. The residue was treated with CH2Cl2 and filtered to give 155 (500 mg, yield 34%) as a white solid. LCMS (ESI), M+H+=450.16. 1HNMR (400 MHz, DMSO) δ 5.875 (s, 2H), 7.046-7.120 (m, 2H), 7.175-7.200 (d, J=1.6 Hz, 1H), 7.242-7.307 (m, 3H), 7.432-7.472 (m, 5H), 7.687-7.708 (d, J=1.2 Hz, 1H), 8.335 (s, 1H)

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08653089B2
Source dataset	uspto-grants-2014_02
ORD ID	ord-1e0826944b4e45a2b1d406495c36873f
Source note	uspto-grants-2014_02