Dichloromethane → Methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	2-Amino-3-chloropyrazine	HCID 276224	—
Reactant	3-Fluoro-4-methoxycarbonylphenylboronic acid, pinacol ester	HCID 22171528	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Product	Methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate	HCID 118045820	84%

Reaction Conditions

Temperature	100 °C

Reaction Steps

To 3-chloropyrazin-2-amine (27 g, 208 mmol) in DME (391 mL) and sodium carbonate (66.3 g, 625 mmol) was added methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (64.2 g, 229 mmol) and PdCl2(dppf).CH2Cl2 adduct (8.51 g, 10.42 mmol). The reaction mixture was purged with N2 and heated in oil bath at 100° C. for 3h. The reaction mixture was partitioned between EtOAc and water. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product was recrystallized by EtOAc and heptane (2:3) to give methyl 4-(3-aminopyrazin-2-yl)-2-fluorobenzoate in 84% yield. LCMS (m/z): 248.1 (MH+), 0.58 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09242996B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-3c8108b0520048ff9cc01e0f663f045b
Source note	uspto-grants-2016_01