3-Aminopyridine → (S)-1-(4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-3-yl)urea

Participants

Reaction Steps

To an ice cold solution of (S)-4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)aniline hydrochloride (0.217 g, 0.47 mmol) in THF/pyridine (4:1 respective ratio, 10 ml) was added triphosgene (1 eq) portionwise. The resulting suspension was stirred for five minutes before adding to an ice cold solution of 3-aminopyridine (4 eq) in THF/pyridine (4:1 respective ratio, 2 ml). The reaction was stirred at 0° C. for 1 hr after which time it was quenched by addition of methanol and concentrated in vacuo. The residue was purified by high pH preparative HPLC to afford the title compound, (S)-1-(4-(4-(3-methylmorpholino)-6-(2-(methylsulfonyl)phenyl)-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-3-yl)urea, 24 mg, 38% yield. 1H NMR (400 MHz, MeOD) δ 8.63 (d, 1H), 8.38-8.33 (m, 2H), 8.19 (dd, 1H), 8.18-8.10 (m, 1H), 8.02 (ddd, 1H), 7.82 (td, 1H), 7.77-7.68 (m, 2H), 7.60-7.56 (m, 2H), 7.38 (dd, 1H), 5.17-4.37 (m, 2H), 3.99 (br s, 1H), 3.84-3.67 (m, 2H), 3.57 (t, 1H), 3.48 (s, 3H), 3.38 (dd, 1H), 1.39 (d, 3H);

Provenance & Evidence