Water → 5-bromo-1-methyl-3-[[5-[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]pyridin-2-one

Participants

Role	Name	HCID	Charge
Reactant	Water	HCID 962	—
Reactant	Sodium cyanoborohydride	HCID 5003444	—
Reactant	3-Oxetanone	HCID 15024254	—
Reactant	(R)-5-Bromo-3-(5-(2,4-dimethylpiperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one	HCID 86683720	—
Catalyst	Zincchloride	HCID 3007855	—
Solvent	Methanol	HCID 887	—
Product	5-bromo-1-methyl-3-[[5-[(2R)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridyl]amino]pyridin-2-one	HCID 86683744	76%

Reaction Conditions

Temperature	50 °C

Reaction Steps

A mixture of 115e (40.0 g, 106 mmol), oxetan-3-one (11.4 g, 159 mmol), NaBH3CN (10.0 g, 159 mmol), and zinc chloride (21.3 g, 159 mmol) in methanol (700 mL) was stirred at 50° C. for 5 hours. water (50 mL) was added to the mixture and concentrated under reduced pressure. The residue was extracted with dichloromethane (3×200 mL) and the combined organic layer was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 40:1 dichloromethane/methanol to afford 115f (35 g, 73%). MS: [M+H]+ 434.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US08729072B2
Source dataset	uspto-grants-2014_05
ORD ID	ord-d2286580d7494f38858527b8acbdcea5
Source note	uspto-grants-2014_05