Dichloromethane → Methyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate

Participants

Role	Name	HCID	Charge
Reactant	Dichloromethane	HCID 6344	—
Reactant	Sodium Carbonate	HCID 10340	—
Reactant	8-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,4-dioxaspiro(4.5)dec-7-ene	HCID 3697076	—
Reactant	Methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate	HCID 118046172	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Solvent	1,2-Dimethoxyethane	HCID 8071	—
Product	Methyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate	HCID 118045608	75%

Reaction Conditions

Temperature	100 °C

Reaction Steps

To a solution of methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (10 g, 30.7 mmol) in DME (77 mL) was added 4,4,5,5-tetramethyl-2-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)-1,3,2-dioxaborolane (9.79 g, 36.8 mmol), PdCl2(dppf).CH2Cl2 adduct (1.252 g, 1.533 mmol), H2O (25.6 mL) and then last sodium carbonate (9.75 g, 92 mmol). The reaction was heat at 100° C. in oil bath for 2 h. Cooled down. The reaction mixture was extracted by EtOAc 3 times, the organic was washed with water and brine, dried and concentrated. The crude material was recrystallized in DCM and heptane (1:1) to give product methyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate in 75% yield. LCMS (m/z): 382.2 (MH+), 0.82 min.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09242996B2
Source dataset	uspto-grants-2016_01
ORD ID	ord-6b3206fe38aa4597ba2cf56b3c788984
Source note	uspto-grants-2016_01