Dichloromethane → 2,5-Dichloro-4-(6-fluoropyridin-2-yl)pyrimidine

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	2,4,5-Trichloropyrimidine	HCID 237259	—
Reactant	2-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine	HCID 42614576	—
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	2,5-Dichloro-4-(6-fluoropyridin-2-yl)pyrimidine	HCID 86650606	72.3%

Reaction Conditions

Temperature	80 °C

Reaction Steps

A mixture of 2,4,5-trichloropyrimidine (49.3 mg, 0.269 mmol), 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (50 mg, 0.224 mmol), PdCl2(dppf).CH2Cl2 adduct (18.31 mg, 0.022 mmol), DME (0.7 ml), and 2M sodium carbonate (0.247 ml, 0.493 mmol) reaction mixture was stirred at about 80° C. until the reaction mixture was complete, as indicated by LCMS. The reaction mixture was cooled, diluted with 5 ml of ethyl acetate and 1 ml of methanol, filtered and concentrated to yield a crude solid. The crude material was purified by silica gel chromatography using a 12 g column, eluting from 0%-40% ethyl acetate with hexane. The desired fractions were concentrated to constant mass, to yield 39.5 mg of titled compound as a free base. LCMS (m/z): 244.0 (MH+), retention time=0.89 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08778951B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-0c060a95a65040b5a10b058dcf168471
Source note	uspto-grants-2014_07