1,2-Dimethoxyethane → methyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate

Participants

Role	Name	HCID	Charge
Reactant	1,2-Dimethoxyethane	HCID 8071	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	3-Fluoro-4-methoxycarbonylphenylboronic acid, pinacol ester	HCID 22171528	—
Reactant	3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyrazin-2-amine	HCID 118045662	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	methyl 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoate	HCID 118045986	67%

Reaction Conditions

Temperature	120 °C

Reaction Steps

To a solution of methyl 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (259 mg, 1.308 mmol), 3-bromo-5-(tetrahydro-2H-pyran-4-yl)pyrazin-2-amine (225 mg, 0.872 mmol), and PdCl2(dppf) (64 mg, 0.087 mmol) was added DME (6.5 mL) and 2 M Na2CO3 solution (3.2 mL). The reaction mixture was heated at the microwave synthesizer (120° C., 10 min). The reaction mixture was worked up with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography (gradient EtOAc in heptane) to yield the desired product (192 mg, 67%). LCMS (m/z): 332.2 (MH+), 0.63 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09242996B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-29476fdb85774640a1dcd70fb79e76d4
Source note	uspto-grants-2016_01