Nitrogen → 1-(Cyclopropylmethyl)-5-[5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-3-methylpyridin-2-one

Participants

Role	Name	HCID	Charge
Reactant	Nitrogen	HCID 947	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	4-Chloro-5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidine	HCID 118021544	—
Reactant	1-(Cyclopropylmethyl)-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(1H)-pyridinone	HCID 123381454	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Ethyl Acetate	HCID 8857	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	1-(Cyclopropylmethyl)-5-[5-(2,4-difluorophenoxy)-2-methylsulfonylpyrimidin-4-yl]-3-methylpyridin-2-one	HCID 118022059	79.3%

Reaction Conditions

Temperature	70 °C

Reaction Steps

The title compound of Example 149, step 3 (200 mg, 0.62 mmol), the title compound of step 2 (250 mg, 0.69 mmol, 70% purity), Pd(dppf)Cl2 (88 mg, 0.12 mmol) and K3PO4 (3 M, 0.6 mL) in dioxane (6 mL) were purged with N2 and heated to 70° C. for 4 h. After silica gel chromatography (PE:EA=3:1˜1:1) the title compound (220 mg, yield: 78.8%) was obtained as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 7.45 (d, J=2.0 Hz, 1H), 8.25 (s, 1H), 8.16 (s, 1H), 7.24-7.22 (m, 1H), 7.12-7.10 (m, 1H), 7.10-7.03 (m, 1H), 3.92 (d, J=7.2 Hz, 2H), 3.38 (s, 3H), 2.26 (s, 3H), 1.27-1.21 (m, 1H), 0.65-0.60 (m, 2H), 0.42-0.38 (m, 2H). LCMS: 448.1 (M+H)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09034900B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-a917a48a4401414f9138f61b42ebc0ea
Source note	uspto-grants-2015_05