Dichloromethane → 5'-Chloro-2'-fluoro-N-[(oxan-4-yl)methyl][2,4'-bipyridin]-6-amine

https://huagongshe.com/reaction/1963808

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	(5-Chloro-2-fluoropyridin-4-yl)boronic acid	HCID 44754822	—
Reactant	HCID 58127218	HCID 58127218	—
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	5'-Chloro-2'-fluoro-N-[(oxan-4-yl)methyl][2,4'-bipyridin]-6-amine	HCID 58127102	80.8%

Reaction Steps

A mixture of 6-bromo-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (C, 271 mg, 1 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (351 mg, 2.000 mmol), PdCl2(dppf).CH2Cl2 adduct (82 mg, 0.100 mmol) in DME (4.5 mL) and 2M Na2CO3 (318 mg, 3.00 mmol) was heated in a sealed tube at about 103° C. for about 2 hr. The mixture then was cooled to ambient temperature, diluted with EtOAc (˜25 mL) and MeOH (˜5 mL), filtered, and concentrated in vacuo to yield a resulting residue. The resulting residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane=10/90 to 50/50]. Fractions were combined and concentrated in vacuo providing 5′-chloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine (260 mg) as a yellow thick oil. LCMS (m/z): 322.1/323.9 [M+H]+; Retention time=0.60 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08415381B2
Source dataset	uspto-grants-2013_04
ORD ID	ord-916693c092a54ab3a9b5483c6a32a603
Source note	uspto-grants-2013_04