2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → Isopropyl 4-(6-(6-bromo-2,4-dimethylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (2.0 g, 6.1 mmol) in 10 ml of dioxane, were added 6-bromo-2,4-dimethylpyridin-3-amine (1.0 g, 5.1 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (0.35 g, 1.0 mmol), Pd(OAc)2 (0.11 g, 0.51 mmol), and NaO-t-Bu (1.2 g, 12 mmol) at an ambient temperature. The reaction was heated to 150° C. for 3 hrs. The reaction was cooled to room temperature and poured into H2O. The organics were extracted with ethyl acetate and dried over MgSO4. The ethyl acetate was concentrated under vacuum and purified over SiO2 to give isopropyl 4-(6-(6-bromo-2,4-dimethylpyridin-3-ylamino)-5-methoxy pyrimidin-4-yloxy)piperidine-1-carboxylate. 1HNMR (CDCl3, 400 MHz) δ 1.24-1.25 (d, J=6.2 Hz, 6H), 1.72-1.77 (m, 2H), 1.95-2.01 (m, 2H), 2.22 (s, 3H), 2.52 (s, 3H), 3.37-3.44 (m, 2H), 3.73-3.79 (m, 2H), 4.91-4.97 (m, 1H), 5.30-5.35 (m, 1H), 6.01 (s, 1H), 7.34-7.36 (d, J=8.5 Hz, 1H), 8.14-8.16 (d, J=8.5 Hz, 1H), 8.37 (s, 1H). Exact mass calculated for C21H28BrN5O4 494.31. found 495.2 (MH+).

Provenance & Evidence