Potassium Phosphate, Tribasic → 4-[5-(Cyclopropylmethoxy)-2-methylsulfonylpyrimidin-4-yl]-2-methyl-5,6,7,8-tetrahydroisoquinolin-1-one

Participants

Role	Name	HCID	Charge
Reactant	Potassium Phosphate, Tribasic	HCID 62657	—
Reactant	1,4-Dioxane--water (1/1)	HCID 21886435	—
Reactant	4-Chloro-5-(cyclopropylmethoxy)-2-methylsulfonylpyrimidine	HCID 118022445	—
Reactant	2-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6,7,8-tetrahydroisoquinolin-1-one	HCID 123801900	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Ethyl Acetate	HCID 8857	—
Product	4-[5-(Cyclopropylmethoxy)-2-methylsulfonylpyrimidin-4-yl]-2-methyl-5,6,7,8-tetrahydroisoquinolin-1-one	HCID 118021972	67%

Reaction Conditions

Temperature	70 °C

Reaction Steps

The title compound of step 3 (200 mg, 0.69 mmol), the title compound of Example 152, step 4 (218 mg, 0.83 mmol), K3PO4 (440 mg, 2.07 mmol) and Pd(dppf)Cl2 (51 mg, 0.7 mmol) in 6:1 dioxane/water (7 mL) were purged with nitrogen and heated at 70° C. for 8 h. After silica gel chromatography (PE:EA=1:1), the title compound (180 mg, yield: 67%) was obtained as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ 8.42 (s, 1H), 7.48 (s, 1H), 4.04 (d, J=7.2 Hz, 2H), 3.60 (s, 3H), 3.35 (s, 3H), 2.65-2.62 (m, 2H), 2.54-2.50 (m, 2H), 1.80-1.78 (m, 2H), 1.77-1.67 (m, 2H), 1.28-1.25 (m, 1H), 0.73-0.71 (m, 2H), 0.41-0.38 (m, 2H).

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09034900B2
Source dataset	uspto-grants-2015_05
ORD ID	ord-b9342e73ef8b453a92c329a98f0a7ce4
Source note	uspto-grants-2015_05