反应详情

温度

100 °C

N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (1.60 g, 4.22 mmol), 8-(5-bromo-1,3-thiazol-2-yl)-1,4-dioxaspiro[4.5]decane-8-carbonitrile (1.40 g, 4.22 mmol), cesium carbonate (4.12 g, 12.6 mmol), Pd2(dba)3 (193 mg, 0.21 mmol) and X-Phos (201 mg, 0.42 mmol) were added to a flame-dried flask, deoxygenated, and diluted with anhydrous 1,4-dioxane (15 ml) and water (1.5 ml). The resulting dark mixture was heated to 100° C. for 5 h. The reaction mixture was diluted with 1:1 saturated aqueous NaHCO3: brine (100 ml) and extracted with EtOAc (2×85 ml). The organic layers were dried over Na2SO4, filtered and concentrated. The crude dark maroon oil was purified via flash column chromatography (SiO2: 100% Hex to 60:40 Hex:EtOAc) which afforded 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carbonitrile (1.77 g, 3.35 mmol, 79% yield) as an off-white solid. MS ESI: [M+H]+ m/z 502.1. 1H NMR (500 MHz, CD3OD): δ 11.1 (s, 1H), 9.65 (d, 1H, J=4.9 Hz), 8.93 (s, 1H), 8.83 (s, 1H), 8.30 (s, 1H), 8.10 (d, 1H, J=4.9 Hz), 8.02 (s, 1H), 4.73-4.72 (m, 4H), 3.21-3.18 (m, 2H), 3.13 (s, 3H), 3.01-2.97 (m, 2H), 2.69-2.61 (m, 4H). rhSYK activity=+++

1. customdeoxygenated
2. additiondiluted with anhydrous 1,4-dioxane (15 ml) and water (1.5 ml)
3. additionThe reaction mixture was diluted with 1:1 saturated aqueous NaHCO3
4. extractionbrine (100 ml) and extracted with EtOAc (2×85 ml)
5. dry with materialThe organic layers were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude dark maroon oil was purified via flash column chromatography (SiO2: 100% Hex to 60:40 Hex:EtOAc) which