Cesium carbonate → {1-[4-(Isoquinolin-6-ylamino)-1-(4-methoxy-phenyl)-cyclohexyl]-propyl}-carbamic acid benzyl ester

Temperature

100 °C

In 1 mL of absolute toluene were dissolved 66.0 mg (0.32 mmol) of 6-bromo-isoquinoline, 151 mg (380 μmol) of {1-[4-amino-1-(4-methoxy-phenyl)-cyclohexyl]-propyl}-carbamic acid benzyl ester (98), and 155 mg (476 μmol) of cesium carbonate. The solution was degassed twice, then 2.14 mg (9.5 μmol) of palladium acetate and 8.89 mg (14.3 μmol) of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were added and the reaction mixture was heated to 100° C. until complete conversion could be observed. The mixture was evaporated, then redissolved in 50 mL of dichloromethane and washed twice with 50 mL of saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, filtered, concentrated and purified by silica gel chromatography (dichloromethane:methanol) to give 48 mg of the pure desired product. Rt=1.38 min (Method 19). Detected mass: 524.4 (M+H+).

1. customThe solution was degassed twice
2. customThe mixture was evaporated
3. dissolutionredissolved in 50 mL of dichloromethane
4. washwashed twice with 50 mL of saturated aqueous sodium bicarbonate solution
5. dry with materialThe organic phase was dried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated
8. custompurified by silica gel chromatography (dichloromethane:methanol)

ORD record

ord-c82a7faf1ea04e85bdff193acf86afb6

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08541449B2