Dichloromethane → 3-chloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	2-Fluoropyridine-4-boronic acid	HCID 2783396	—
Reactant	6-bromo-5-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine	HCID 58127341	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Methanol	HCID 887	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	3-chloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine	HCID 66937054	77.8%

Reaction Steps

A mixture of 6-bromo-5-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (intermediate E) (630 mg, 2.062 mmol), 2-fluoropyridin-4-ylboronic acid (639 mg, 4.54 mmol), PdCl2(dppf).CH2Cl2 adduct (168 mg, 0.206 mmol), DME (9 ml) and 2M sodium carbonate (3.09 ml, 6.18 mmol) was stirred at 105° C. for 2 hours, and the reaction progress was followed by LCMS. The reaction mixture was let cool to room temperature, diluted with 30 ml of ethyl acetate, 10 ml of methanol, filtered and concentrated. The crude material was purified by silica gel chromatography using 40 g column and eluting with 5-45% ethyl acetate in heptane. The desired fractions were concentrated to constant mass giving, 516 mg of the title compound as free base. LCMS (m/z): 332.0 (MH+), retention time=0.88 min

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08778951B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-3b42f88953844012abf2c25bea0721a3
Source note	uspto-grants-2014_07