1,4-Dioxane → 2-(4-((3-(2-Methylpyridin-4-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline

Participants

Role	Name	HCID	Charge
Reactant	1,4-Dioxane	HCID 31275	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	3-Methyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine	HCID 45588135	—
Reactant	2-(4-((3-Chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline	HCID 58547687	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Product	2-(4-((3-(2-Methylpyridin-4-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline	HCID 58547972	60%

Reaction Conditions

Temperature	110 °C

Reaction Steps

To a solution of 2-(4-((3-chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P2.1; 340 mg, 1.0 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (see PREPARATION P12.1; 219 mg, 1.0 mmol) and K3PO4 (424 mg, 2.0 mmol) in 1,4-dioxane (10 mL) and H2O (2 mL) was added Pd(dppf)Cl2 (73 mg, 0.1 mmol) then the reaction mixture was stirred at 110° C. under N2 atmosphere overnight. The reaction mixture was filtered through CELITE® and washed with CH2Cl2 (30 mL). The filtrate was concentrated and the crude product was purified by silica gel column to give 2-(4-((3-(2-methylpyridin-4-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline (200 mg, 0.50 mmol, yield 60%). ESI-MS (M+1): 398 calc. for C24H23N5O 397.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08497265B2
Source dataset	uspto-grants-2013_07
ORD ID	ord-8a89b79c29f84842abea64d568ae861c
Source note	uspto-grants-2013_07