Cesium carbonate → HCID 86712670, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of methyl 2-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetate (K7) (110 mg, 0.366 mmol) in 1,4-dioxane (5 mL) was added tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (101 mg, 0.366 mmol), Cs2CO3 (477 mg, 1.46 mmol), Pd2(dba)3 (33 mg, 0.037 mmol) and Xantphos (63 mg, 0.11 mmol). The resulting suspension was degassed with nitrogen for 5 minutes then heated under microwave irradiation for 30 minutes at 120° C. The volatiles were removed under reduced pressure and the residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give a yellow oil. A suspension of 10% Pd/C (100 mg) in DMF (10 mL) and Et3N (1 mL) was added and the resulting mixture stirred under an atmosphere of hydrogen for 16 hours. EtOAc (60 mL) was added and the resulting mixture filtered through Celite. The filtrate was evaporated under reduced pressure and the residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridges, 0-60% EtOAc in petroleum benzine 40-60° C.) to give a yellow oil. This was taken up in THF (7 mL), MeOH (7 mL) and H2O (1.5 mL) to which LiOH.H2O (115 mg, 2.74 mmol) was added. The resulting mixture was stirred at room temperature overnight then the volatiles were removed under reduced pressure. The residue was partitioned between EtOAc (50 mL) and aqueous HCl (2 M; 50 mL) then the layers were separated. The aqueous phase was extracted with EtOAc (2×50 mL) then the organics were combined, washed with brine and dried over MgSO4. The volatiles were removed in vacuo to give the title compound A55 as yellow oil (127 mg, 87%); LCMS-A: rt 6.272 min; m/z 531 [M+H]+.

Provenance & Evidence