Nitrogen → 4-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one

Participants

Role	Name	HCID	Charge
Reactant	Nitrogen	HCID 947	—
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	2-Bromo-4-ethylsulfonyl-1-methoxybenzene	HCID 10978809	—
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	Water	HCID 962	—
Solvent	1,4-Dioxane	HCID 31275	—
Product	4-[5-(ethylsulfonyl)-2-methoxyphenyl]-2-methyl-6-(1-methyl-1H-pyrazol-4-yl)isoquinolin-1(2H)-one	HCID 118021476	55.7%

Reaction Steps

For 5 min N2 was bubbled into a mixture of 2-bromo-4-ethylsulfonyl-1-methoxybenzene (300 mg, 1.07 mmol), the title compound of Example 46, step 2 (300 mg, 0.82 mmol), K3PO4 (435.6 mg, 2.05 mmol) and Pd(dppf)Cl2 (120.2 mg, 0.16 mmol) in dioxane (8 mL) and water (0.8 mL) which was then microwaved at 110° C. for 30 min. Purification by silica gel chromatography (DCM:MeOH=100:0 to 20:1) gave the title compound (200 mg, 55.7%) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ 8.51 (d, J=8.4 Hz, 1H), 8.03 (dd, J1=8.8 Hz, J2=2.8 Hz, 1H), 7.86 (d, J=2.4 Hz, 1H), 7.72 (s, 1H), 7.64 (s, 1H), 7.63-7.61 (m, 1H), 7.19 (d, J=8.8 Hz, 1H), 7.15 (d, J=1.2 Hz, 1H), 7.09 (s, 1H), 3.97 (s, 3H), 3.85 (s, 3H), 3.68 (s, 3H), 3.18 (q, J=7.6 Hz, 2H), 1.35 (t, J=7.6 Hz, 3H). LCMS: 438.1 (M+H)+

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09034900B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-380a627aeeb7496182924a2f356bab34
Source note	uspto-grants-2015_05