反应详情

To a mixture of (1R,2S)-2-(3-iodo-1H-indazol-6-yl)-5′-methoxyspiro [cyclopropane-1,3′-indolin]-2′-one (172 mg, 0.4 mmol) and (E)-4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)phenethyl)morpholine (138 mg, 0.4 mmol) in PhCH3/EtOH (8 mL/4 mL) in a 20 mL microwave vial was added 1 M Na2CO3 (0.8 mL, 0.8 mmol), followed by Pd(PPh3)4 (23 mg, 0.02 mmol, 5 mol %). The resulting mixture was purged with argon, then microwaved for 2 h at 125° C. After cooling to rt, the mixture was diluted with H2O (20 mL), extracted with EtOAc (30 mL×2) and dried (Na2SO4). After removal of solvents, the residue was redissolved in DMF (4 mL) and purified by preparatory HPLC to give the title compound (TFA salt, 115 mg, 45%) as a pale yellow solid. 1H NMR (400 MHz, CD3OD) δ 7.90 (d, J=8.4 Hz, 1H), 7.53 (d, J=7.2 Hz, 2H), 7.43 (s, 1H), 7.37 (d, J=6.4 Hz, 2H), 7.28 (d, J=7.2 Hz, 2H), 6.95 (d, J=7.6 Hz, 1H), 6.81 (d, J=8.4 Hz, 1H), 6.57 (d, J=7.6 Hz, 1H), 5.57 (s, 1H), 4.06 (d, J=11.2 Hz, 2H), 3.80 (t, J=11.2 Hz, 2H), 3.56 (d, J=11.2 Hz, 2H), 3.38 (t, J=7.6 Hz, 2H), 3.27-3.12 (m, 5H), 3.07 (t, 2H), 2.20-2.10 (m, 2H); MS ESI 521.4 [M+H]+, calcd for [C32H32N4O3+H]+ 521.2.

1. customThe resulting mixture was purged with argon
2. custommicrowaved for 2 h at 125° C
3. additionthe mixture was diluted with H2O (20 mL)
4. extractionextracted with EtOAc (30 mL×2)
5. dry with materialdried (Na2SO4)
6. customAfter removal of solvents
7. dissolutionthe residue was redissolved in DMF (4 mL)
8. custompurified by preparatory HPLC