Cesium carbonate → HCID 59145171, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of the above amine (235 mg, 1.71 mmol), 5-bromo-thiophene-2-carboxylic acid methyl ester (565 mg, 2.56 mmol), Pd2(dba)3 (31 mg, 0.03 mmol), XantPhos (49 mg, 0.09 mmol) and Cs2CO3 (1.1 g, 3.42 mmol) in dioxane was heated in a pressure vessel at 130° C. After 13 hours, the reaction mixture was diluted with dioxane/THF (1:1, 40 mL) and stirred. The mixture was then filtered through celite pad and washed with DCM/THF. The filtrate was then concentrated and used further without purification. MS found for C17H18FN5O2S as (M+H)+ 376.15. To the above crude ester in MeOH/THF (1:1) (10 mL) was added 3N NaOH (4.0 mL) and stirred at 55° C. After 16 hours, the reaction mixture was concentrated, diluted with water and washed with ether (3×). The aqueous phase was then neutralized with 6N HCl (1.5 mL) and the precipitated solid was dried to give 5-[5-fluoro-4-(3-isopropyl-2-methyl-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-thiophene-2-carboxylic acid which was used for the next step without purification. MS found for C16H16FN5O2S as (M+H)+ 362.07.

Provenance & Evidence