Compound having kinase inhibitory activity, and preparation method and use thereof
A technology of compounds and solvates, applied in the field of compounds with kinase inhibitory activity, can solve problems such as uncontrolled cell proliferation
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0205] The preparation of formula I compound
[0206] The present invention provides a kind of method for preparing formula I compound, it is characterized in that, described method comprises steps:
[0207] a1) coupling a compound of formula 1a with a compound of formula 3a or a compound of formula 2a with a compound of formula 4a under reaction conditions in the presence of a metal catalyst or acid / base to form intermediate 5a; and
[0208] a2) Coupling the intermediate 5a and the compound of formula 6a under the reaction conditions in the presence of a catalyst to obtain the compound of formula I;
[0209]
[0210] of all kinds,
[0211] X and LG are each independently a leaving group selected from the group consisting of halogen, sulfonate, boronic acid, borate;
[0212] FG is selected from the group consisting of boric acid, borate ester, boron salt, organotin, organozinc;
[0213] The definitions of other groups R1, R2, R3, R4, M, M1, M2, M3, M4, M5, L, W and m, n ...
Embodiment 1
[0377]
[0378] Add 6-(6-chloro-pyrimidin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole (50 mg, 0.155mmol), tris(dibenzylideneacetone)dipalladium (14mg, 0.015mmol), 5-chloropyrazin-2-amine (24mg, 0.186mmol), 4,5-bisdiphenylphosphine-9,9 - Dimethylxanthene (17 mg, 0.029 mmol), cesium carbonate (101 mg, 0.31 mmol) and dry dioxane (1 mL), replaced with nitrogen 3 times. Microwave at 120°C for 2 hours. Add 10 mL of water to the reaction solution, extract with dichloromethane (20 mL*3), combine the organic phases, wash with 20 mL of saturated brine, dry over anhydrous sodium sulfate, filter, and concentrate the filtrate under reduced pressure. Purification by chromatography affords the title compound. LCMS: 498(M+H); 1 H-NMR (400MHz, DMSO-d 6 )δ10.71(s,1H),9.12(s,1H),8.89(s,1H),8.55(s,1H),8.20(s,1H),8.02(s,1H),7.62(d,J =11.6Hz,1H),7.93(d,J=1.2Hz,1H),7.63(s,1H),4.82-4.89(m,1H),2.64(s,3H),1.63(d,J=6.8Hz ,6H).
Embodiment 2
[0380]
[0381]With 6-(6-chloro-5-fluoropyridin-4-yl)-4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazole (50mg, 0.155mmol) and 5- ((4-Ethylpiperazin-1-yl)methyl)pyrazin-2-amine (41mg, 0.186mmol) is a raw material, and the same method as in Example 1 is used to synthesize the target compound N-(5-((4 -Ethylpiperazin-1-yl)methyl)pyrazin-2-yl)-5-fluoro-6-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d] imidazol-6-yl)pyrimidin-4-amine (30mg). LCMS: 508.2 (M+H)+. 1 H-NMR (400MHz, DMSO-d 6 )δ10.39(s,1H),9.29(s,1H),8.63(s,1H),8.42(s,1H),8.15(s,1H),7.64(d,J=12.4Hz,1H), 4.83-4.86(m,1H),3.62(s,2H),2.64(s,3H),2.38-2.46(m,8H),2.27-2.33(m,2H),1.60(d,J=7.2Hz, 6H), 0.97(t, J=7.2Hz, 3H).
[0382] Using the above-mentioned different synthetic building blocks as raw materials, the same synthetic method as in Example 1 was used to prepare the following compounds:
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More