HCID 58065794, compound → HCID 56644515, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(2,2,6,6-tetramethylpiperidin-4-ylamino)-2-chloropyrimidine-5-carbonitrile (112 mg, 0.380 mmol, 1 equiv), 3-cyclopropyl-4-fluoro-5-(1H-tetrazol-1-yl)benzenamine (100 mg, 0.456 mmol, 1.2 equiv), and PTSA monohydrate (58 mg, 0.304 mmol, 0.8 equiv) in IPA (4 mL) were heated to 60° C. for 5 days. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The residue was taken in ice-cold water and EtOAc then adjusted to ca. pH 12-14 with 1N NaOH. The aqueous and organic layers were partitioned, and the aqueous layer was extracted with EtOAc (1×150 mL). The combined organic extracts were dried (Na2SO4), filtered, and the solvent removed under vacuum. The crude product was submitted to the analytical department for purification by reverse-phase HPLC using 0.1% formic acid as a modifier in water and acetonitrile (compound unstable in TFA). The product as the formate salt was taken in ice-cold water and EtOAc then adjusted to ca. pH 12-14 with 1N NaOH. The aqueous and organic layers were partitioned, and the aqueous layer was extracted with EtOAc (2×150 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated to give desired compound (63 mg, 35%) as a solid.

Provenance & Evidence