Reacción #1487153

Ecuación de reacción

Intermediate 3

1-(7-bromo-5-iodobenzothiazol-2-yl)-3-ethylurea

iv

Ethyl 4-methyl-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)piperidine-4-carboxylate

MeOH

potassium phosphate

→

Intermediate 7

Rendimiento 41.2%

Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzothiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Rendimiento 41.2%

Disolventes

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe resulting mixture was degassed for 15-20 min
2. 2
   Otroby purging N2
3. 3
   OtroThe reaction mixture was again degassed for another 15-20 min
4. 4
   TemperaturaThe reaction mixture was cooled to RT
5. 5
   workup.ADDITIONdiluted with EtOAc (500 mL)
6. 6
   OtroThe filtrate was evaporated
7. 7
   Otrothe crude residue was purified by chromatography on silica eluting with 1.5% MeOH

Procedimiento

To a solution of Intermediate 3 (22.7 g, 53.2 mmol) and iv (20 g, 53.2 mmol) in 1,4-dioxane:MeOH (300:180 mL) was added potassium phosphate (17 g, 79 mmol) at RT. The resulting mixture was degassed for 15-20 min by purging N2 followed by the addition of Pd(PPh3)4 (6.1 g, 5.32 mmol). The reaction mixture was again degassed for another 15-20 min and then heated up to 80° C. for 5 h. The reaction mixture was cooled to RT, diluted with EtOAc (500 mL) and passed through celite bed. The filtrate was evaporated and the crude residue was purified by chromatography on silica eluting with 1.5% MeOH:DCM to obtain Intermediate 7 (12 g, 41%).

Fuente