2-aminopyrimidine heterocyclic compound and application
A technology of heterocyclic compounds and aminopyrimidines, applied in the field of medicine, can solve the problem of whether CDK4CDK9 is effective or not, and achieve the effect of great clinical application value and considerable market potential.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0086] Example 1 Compound BT-B-1: N-(3-fluoro-4-piperidine-methyl)phenyl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl -1H-Benzo[d]imidazol-6-yl)pyrimidin-2-amine
[0087]
[0088] The synthetic route of compound BT-B-1 is as follows:
[0089]
[0090] Intermediate A1 (322mg, 1mmol), Intermediate B1 (208mg, 1mmol), cesium carbonate (651mg, 2mmol), 4,5-bisdiphenylphosphine-9,9-dimethylxanthene (Xantphos, 116mg ,0.2mmol) was dissolved in 1,4-dioxane (10mL), and tris(dibenzylideneacetone)dipalladium (Pd 2 (dba) 3 , 183mg, 0.2mmol), reacted at 90°C for 3 hours until the reaction was complete, cooled the reaction solution to room temperature and poured it into 10mL water, extracted three times with ethyl acetate (30mL×3), combined the organic phase, and used saturated brine (50mL) for the organic phase Washed, dried with anhydrous sodium sulfate, filtered, spin-dried, and the solid was purified with silica gel column (DCM:CH 3 OH=20:1), a yellow solid was obtained, namely th...
Embodiment 2
[0125] Example 2 Compound BT-B-2: N-(4-((4-dimethylamino)piperidin-1-yl)methyl)-3-fluorophenyl)-5-fluoro-4-(4- Fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine
[0126]
[0127] The synthetic route of compound BT-B-2 is as follows:
[0128]
[0129] Referring to the synthesis method of BT-B-1 in Example 1, a yellow solid can be obtained, which is the target compound BT-B-2.
[0130] MS(m / z): 538.3[M+H] + .
[0131] 1 H NMR (400MHz, DMSO-d6) δppm 10.00 (s, 1H), 8.69 (d, J = 4.0Hz, 1H), 8.23 (d, J = 0.8Hz, 1H), 7.79 (dd, J = 12.8, 2.0 Hz, 1H), 7.66(d, J=12.0Hz, 1H), 7.47(dd, J=8.8, 2.4Hz, 1H), 7.27(t, J=8.4Hz, 1H), 4.85(p, J=6.8 Hz,1H),3.43(s,2H),2.85(m,2H),2.65(s,3H),2.16(s,6H),2.03(m,1H),1.93(m,2H),1.69(m , 2H), 1.62 (d, J=6.8Hz, 6H), 1.35 (m, 2H).
[0132] The synthetic route and synthetic steps of intermediate A1 are the same as the synthetic route and synthetic steps of A1 in Example 1, and will not be repeated here.
[0133] The synthe...
Embodiment 3
[0137] Example 3 Compound BT-B-3: N-(3-fluoro-4-(morpholin-1-ylmethyl)phenyl)-5-fluoro-4-(4-fluoro-1-isopropyl- 2-Methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine
[0138]
[0139] The synthetic route of compound BT-B-3 is as follows:
[0140]
[0141] Referring to the synthesis method of BT-B-1 in Example 1, a yellow solid can be obtained, which is the target compound BT-B-3.
[0142] MS(m / z): 497.3[M+H] + .
[0143] 1 H NMR(400MHz,DMSO-d6)δppm 10.00(s,1H),8.68(d,J=3.6Hz,1H),8.23(s,1H),7.81(dd,J=13.2Hz,2.0Hz,1H) ,7.66(d,J=12.0Hz,1H),7.48(dd,J=8.4Hz,2.0Hz,1H),7.29(t,J=8.4Hz,1H),4.85(p,J=6.8Hz,1H ), 3.56(t, J=4.4Hz, 4H), 3.46(s, 2H), 2.65(s, 3H), 2.37(t, J=4.4Hz, 4H), 1.62(d, J=6.8Hz, 6H ).
[0144] The synthetic route and synthetic steps of intermediate A1 are the same as the synthetic route and synthetic steps of A1 in Example 1, and will not be repeated here.
[0145] The synthetic route of intermediate B3 is as follows:
[0146]
[0147] With reference to t...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More