HCID 178484568, compound → HCID 89924329, compound

Participants

Reaction Steps

Trimethylaluminium (1.50 mL; 3.0 mmol; 5.4 eq.) was added dropwise over 1 min to a solution of dimethylamine (2.50 mL; 5.0 mmol; 9.1 eq.) in DCE (50 mL) at 0° C. After 10 min, 4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanecarboxylic acid ethyl ester (prepared as described in example 62, step; 300 mg; 0.55 mmol; 1.0 eq.) in DCE (50 mL) was added dropwise over 5 min. The reaction solution was stirred for 16 h then a further portion of trimethylaluminium (10 mL; 20 mmol; 36 eq.) was added and the reaction solution refluxed for 4 h. The reaction mixture was then poured into ice-cold MeOH and concentrated under reduced pressure. The residue was redissolved in DCM, washed with 1 N HCl solution, Rochelle's salt solution and brine. Organic phase was finally dried over magnesium sulfate, filtered and concentrated to give the title compounds as a 3:1 mixture of cis and trans 4-(4-{2-[3-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-pyrimidin-5-yl}-pyrazol-1-yl)-cyclohexanecarboxylic acid dimethylamide (165 mg; 60%) in the form of a beige solid. HPLC (Chiralpak IC, EtOH:THF 90:10): Rt 6.61; 10.38 min (purity 76, 24%); MS (ESI+): 456.4.

Provenance & Evidence