Toluene → HCID 178434520, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of (4-hydroxy-piperidin-1-yl)-{4-[4-(4-iodobenzotriazol-1-yl)-pyrimidin-2-yl-amino]-cyclohexyl}-methanone (274 mg) and 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg), Na2CO3 (2 M aq, 0.7 mL, degassed), toluene (9 mL, degassed) and EtOH (0.7 mL) was bubbled with argon in a screw cap pressure flask for 10 min. To this was added Pd(PPh3)4 (18 mg), the flask sealed, and the mixture stirred overnight at 110° C. The reaction mixture was allowed to cool to RT, then additional portions of 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg), Pd(PPh3)4 (20 mg), and EtOH (5 mL) were added, the flask sealed, and heated again at 110° C. for 6 h. An additional portion of 3-methyl-pyrazole-4-boronic acid pinacol ester (109 mg) and Pd(PPh3)4 (20 mg) was added, and the mixture stirred at 110° C. overnight. The reaction mixture was then cooled to RT, diluted in water, extracted in DCM, washed with water and brine, dried over Na2SO4, and the solvent stripped to yield a crude solid (311 mg). The crude product (52 mg) was chromatographed on silica, and eluted with 0-60% Magic Base/DCM, titurated in Et2O overnight, filtered, and dried to yield (4-hydroxy-piperidin-1-yl)-(4-{4-[4-(3-methyl-1H-pyrazol-4-yl)-benzotriazol-1-yl]-pyrimidin-2-ylamino}-cyclohexyl)-methanone (Compound 11, 28 mg). mp=190-195° C.; M+H=502.

Provenance & Evidence