Cesium carbonate → 5-(2-(Hydroxymethyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrile

Participants

Role	Name	HCID	Charge
Reactant	Cesium carbonate	HCID 10796	—
Reactant	2-Cyanopyridine-5-boronic acid pinacol ester	HCID 16414188	—
Reactant	(5-Bromo-8-morpholinoimidazo[1,2-a]pyrazin-2-yl)methanol	HCID 117727888	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane--water (1/1)	HCID 21886435	—
Product	5-(2-(Hydroxymethyl)-8-morpholinoimidazo[1,2-a]pyrazin-5-yl)picolinonitrile	HCID 117727910	54.2%

Reaction Conditions

Temperature	90 °C

Reaction Steps

To a solution of compound 1e (600 mg, 1.92 mmol, as prepared in Step E) in 1,4-dioxane/H2O (4:1 v/v, 8 mL) was added compound 1f (560 mg, 2.44 mmol), PdCl2(dppf) (72.1 mg, 0.0960 mmol) and Cs2CO3 (847 mg, 4.99 mmol). The reaction mixture was stirred at 90° C. for 2 h under a nitrogen atmosphere. After cooling to rt, the reaction was quenched with H2O (20 mL). The resulting mixture was extracted with DCM (2×50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel with EtOAc/petroleum ether (1:2 v/v) to obtain compound 1g as a yellow solid (350 mg, 51% yield). Mass Spectrum (LCMS, ESI pos.): Calcd. for C17H16N6O2: 337.1 (M+H). Found 337.2.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09249163B2
Source dataset	uspto-grants-2016_02
ORD ID	ord-1ffa3dcbae01441b8b03c509c18cc98d
Source note	uspto-grants-2016_02