Imidazole → 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-sulfonamide

Participants

Reaction Steps

A solution of thiazol-2-amine (0.097 g, 0.970 mmol) and imidazole (0.198 g, 2.91 mmol) in 4 mL of DCM was cooled to −78° C. Sulfuryl chloride (0.079 ml, 0.970 mmol) was added, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional 30 minutes. 4-(2-methoxy-4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride (0.150 g, 0.485 mmol) was added, followed by n,n-diisopropylethylamine (0.847 ml, 4.85 mmol), and the reaction mixture was heated to reflux for one hour, after which time the reaction was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18, 30μ 55 g, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-sulfonamide (0.138 g, 0.293 mmol, 60.4% yield). 1H NMR (MeCN-d3) δ: 8.96 (s, 1H), 7.33-7.42 (m, 3H), 6.93 (d, J=4.8 Hz, 1H), 6.55 (d, J=4.8 Hz, 1H), 4.35 (br. s., 2H), 3.79-3.87 (m, 3H), 3.08-3.53 (m, 2H), 2.39-2.89 (m, 1H); (M+H)+=472.0.

Provenance & Evidence