反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
PROCEDURE
实验过程
2-{4-[4-(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino)-phenyl]-piperidin-1-yl}-acetamide (150 mg, 0.00035 mol), 2-Methanesulfonyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-isoindole (169.4 mg, 0.0005241 mol), 0.9 M of Sodium carbonate in water (0.23 mL, 0.00021 mol), Tetrakis(triphenylphosphine)palladium (O) (0.040 g, 0.000035 mol) and Tetrahydrofuran (2 mL, 0.03 mol) were heated at 80° C. overnight. The reaction was cooled to RT, dissolved partially in DCM and filtered. The filtrate was placed onto a 40 gm column eluting with DCM to 5% MeOH/DCM. Dissolved in DMSO, filtered and placed onto the Gilson. Most pure fractions were free based and worked up to give 2-(4-{4-[7-(2-Methanesulfonyl-2,3-dihydro-1H-isoindol-4-yl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-acetamide as a yellow solid (3.7 mg, 1.9%). MP 244-247° C. LCMS (E/I+) 546 (M+H). NMR 1H (DMSO-d6)-9.45 (s, 1H), 9.01 (s, 1H), 7.97 (d, 1H, J=7.77 Hz), 7.62 (d, 2H, J=8.60 Hz), 7.56 (t, 1H, J=7.68 Hz), 7.44 (d, 1H, J=7.54 Hz), 7.20 (s, 1H), 7.12 (s, 1H), 7.10 (d, 1H, J=8.51 Hz), 7.06 (d, 1H, J=4.63 Hz), 6.98 (d, 1H, J=4.80 Hz), 4.74 (s, 4H), 2.91-2.92 (m, 4H), 2.86-2.89 (m, 3H), 2.38-2.42 (m, 1H), 2.10-2.20 (m, 2H), 1.65-1.74 (m, 4H).
WORKUP
后处理
- filtrationfiltered
- washeluting with DCM to 5% MeOH/DCM
- dissolutionDissolved in DMSO
- filtrationfiltered