反应详情

温度

95 °C

N′-[5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]-4-methoxy-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine (Intermediate 74, 268 mg, 0.58 mmol), zinc powder (3.78 mg, 0.06 mmol), tris(dibenzylideneacetone)dipalladium(0) (52.9 mg, 0.06 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (‘XPhos’, 55.1 mg, 0.12 mmol), and dicyanozinc (40.7 mg, 0.35 mmol) were placed in a flask under N2 and then degassed DMA (3 mL) was added. The resulting suspension was stirred for 3 h at 95° C. The mixture was then diluted with EtOAc and washed 5 times with water and then brine. The solution was then dried (MgSO4) and concentrated in vacuo. The resulting residue was triturated with diethyl ether and the resulting solid was collected by filtration and washed with diethyl ether to give crude product. This crude material was dissolved into CH2Cl2/CH3OH and concentrated in vacuo onto silica. Purification by FCC, eluting with 1.5-8% 7N methanolic ammonia in CH2Cl2 provided a solid which was washed with CH3OH (0.2 mL) to give the title compound (48 mg, 18%) as a beige crystalline solid; 1H NMR: 2.26 (3H, s), 2.53 (4H, m), 2.91 (4H, s), 3.65 (3H, s), 4.38 (2H, d), 6.74 (1H, s), 6.85 (1H, s), 6.99 (1H, s), 7.19 (1H, s), 7.48 (1H, d), 8.01 (1H, s), 8.52 (1H, s), 8.65 (1H, s), 9.21 (1H, s), 11.97 (1H, s); m/z: ES+ MH+ 455.

1. washwashed 5 times with water
2. dry with materialThe solution was then dried (MgSO4)
3. concentrationconcentrated in vacuo
4. customThe resulting residue was triturated with diethyl ether
5. filtrationthe resulting solid was collected by filtration
6. washwashed with diethyl ether
7. customto give crude product
8. concentrationconcentrated in vacuo onto silica
9. customPurification by FCC
10. washeluting with 1.5-8% 7N methanolic ammonia in CH2Cl2
11. customprovided a solid which
12. washwas washed with CH3OH (0.2 mL)