Dichloromethane → tert-butyl 5'-chloro-2'-fluoro-2,4'-bipyridin-6-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	1,2-Dimethoxyethane	HCID 8071	—
Reactant	(5-Chloro-2-fluoropyridin-4-yl)boronic acid	HCID 44754822	—
Reactant	tert-butyl 6-bromopyridin-2-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate	HCID 58127385	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	tert-butyl 5'-chloro-2'-fluoro-2,4'-bipyridin-6-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate	HCID 58127426	57%

Reaction Conditions

Temperature	100 °C

Reaction Steps

A mixture of tert-butyl 6-bromo-pyridin-2-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate (50 mg, 0.125 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (43.7 mg, 0.249 mmol), PdCl2(dppf).CH2Cl2 adduct (15.2 mg, 0.019 mmol), DME (1.5 Ml) and 2M aqueous Na2CO2 (0.25 Ml, 0.5 mmol) was sealed and stirred at 100° C. for 3 hours. After cooling to room temperature the mixture was diluted with EtOAc (15 Ml), filtered and concentrated in vacuo. The crude material was purified by column chromatography [silica gel, 12 g, EtOAc/hexane=5/100 to 50/50] to provide tert-butyl 5′-chloro-2′-fluoro-2,4′-bipyridin-6-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate (32 mg, 57% yield). LCMS (m/z): 452.2 [M+H]+; retention time=1.068 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08778951B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-04496030a0b941b79f25df55f93c4892
Source note	uspto-grants-2014_07