Dichloromethane → 6-(5-chloro-2-fluoropyridin-4-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine

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	6-Chloro-N-methyl-N-(tetrahydro-2H-pyran-4-ylmethyl)-2-pyrazinamine	HCID 53410302	—
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	6-(5-chloro-2-fluoropyridin-4-yl)-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine	HCID 66937027	79.6%

Reaction Conditions

Temperature	112.5 °C

Reaction Steps

To 6-chloro-N-methyl-N-((tetrahydro-2H-pyran-4-yl)methyl)pyrazin-2-amine (450 mg, 1.862 mmol) was added 5-chloro-2-fluoropyridin-4-ylboronic acid (588 mg, 3.35 mmol), PdCl2(dppf).CH2Cl2 adduct (182 mg, 0.223 mmol), DME (8 ml) and 2M sodium carbonate (2.79 ml, 5.59 mmol). The resulting reaction mixture was stirred at 110-115° C. for 90 minutes, and the reaction progress was followed by LCMS. The reaction mixture was cooled, 20 ml of ethyl acetate and 10 ml of methanol were added, filtered and concentrated to crude product. The crude was purified by silica gel chromatography using 24 g column eluting with 20-75% ethyl acetate in heptane. The desired fractions were concentrated to constant mass, giving 499 mg of titled compound as free base. LCMS (m/z): 337.1 (MH+), retention time=0.90 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08778951B2
Source dataset	uspto-grants-2014_07
ORD ID	ord-505f8a6fb36c4f81b400bad752c5a12a
Source note	uspto-grants-2014_07