Potassium Phosphate, Tribasic → US10023592, Example 86

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	N-(5-bromo-2-fluoro-4-methoxyphenyl)ethanesulfonamide	HCID 118021927	—
Reactant	2-Methyl-6-(1-methylpyrazol-4-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-1-one	HCID 123751349	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	US10023592, Example 86	HCID 118022248	26.6%

Reaction Steps

A mixture of N-(5-bromo-2-fluoro-4-methoxyphenyl)ethanesulfonamide (63 mg, 0.20 mmol), the title compound of Example 46, step 2 (75 mg, 0.21 mmol), Pd(dppf)Cl2 (19 mg, 0.03 mmol) and aqueous K3PO4 (1 M, 0.5 mL, 0.5 mmol) in dioxane (3 mL) was microwaved at 100° C. for 1 h. Purification by silica gel chromatography (PE:EA=1:1 to 1:4) followed by preparative HPLC gave the title compound (25 mg, 26.3%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.48 (d, J=8.4 Hz, 1H), 7.72 (s, 1H), 7.69 (s, 1H), 7.58 (d, J=7.2 Hz, 1H), 7.49 (d, J=9.2 Hz, 1H), 7.25 (s, 1H), 7.04 (s, 1H), 6.85 (d, J=12.0 Hz, 1H), 6.37 (s, 1H), 3.94 (s, 3H), 3.75 (s, 3H), 3.65 (s, 3H), 3.17 (q, J=7.2 Hz, 2H), 1.46 (t, J=7.2 Hz, 3H). LCMS: 471.1 (M+H)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09115114B2
Source dataset	uspto-grants-2015_08
ORD ID	ord-fc0d3f56d4af4a0c8c02755858553b38
Source note	uspto-grants-2015_08