Potassium Phosphate, Tribasic → US10023592, Example 381

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	1-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one	HCID 45480194	—
Reactant	5-Bromo-4-(cyclopropylmethoxy)-1-(methylsulfonylmethyl)pyridin-2-one	HCID 118021995	—
Catalyst	Water	HCID 962	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	US10023592, Example 381	HCID 118022007	31.5%

Reaction Conditions

Temperature	70 °C

Reaction Steps

The title compound from step 4 (50 mg, 0.15 mmol), 1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (42 mg, 0.18 mmol), Pd(dppf)Cl2 (11 mg, 14.9 umol) and K3PO4 (63 mg, 0.3 mmol) in dioxane (5 mL) and water (5 drops) were degassed and then heated to 70° C. under N2 overnight. The reaction mixture was then concentrated under reduced pressure. The residue was purified by column chromatography (PE:DCM:EA=3:0:1 to 0:1:4) followed by preparative HPLC to afford the title compound (17.09 mg, 31.5%) as an off-white solid. 1H NMR (CDCl3, 400 MHz) δ 7.50 (dd, J1=9.2 Hz, J2=2.4 Hz, 1H), 7.43 (d, J=2.4 Hz, 1H), 6.71 (d, J=9.2 Hz, 1H), 5.96 (s, 1H), 5.16 (s, 2H), 3.86 (d, J=6.8 Hz, 1H), 3.63 (s, 3H), 2.99 (s, 3H), 1.26-1.21 (m, 1H), 0.70-0.66 (m, 2H), 0.36-0.32 (m, 2H). LCMS: 365.0 (M+1)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09034900B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-7185496517304e3f8cbd1b42d971c645
Source note	uspto-grants-2015_05