A kind of pyrimidine derivative and its synthesis method and application

A technology of pyrimidine derivatives and pyrimidine, which is applied in the field of the structure and preparation of pyrimidine derivatives, and can solve problems such as patient drug resistance and drug resistance

CN111171033BActive Publication Date: 2021-11-02TIANJIN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Publication Date
2021-11-02

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Abstract

The invention discloses a pyrimidine derivative and its synthesis method and application. First, an aromatic amine compound 2-phenylpyrimidin[1,2-c]imidazol-7-amine is obtained, and then combined with 2,5-dichloro-N- (2-(isopropylsulfonyl)phenyl)pyrimidine-4-amine obtains pyrimidine derivatives through catalytic coupling reaction. The invention has the advantages of simple preparation process and easy operation. The prepared product has ALK inhibitory activity and can be used to prepare ALK inhibitors.
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Description

technical field

[0001] The invention belongs to the field of medicinal chemistry, and more specifically relates to a structure of a pyrimidine derivative with ALK inhibitory activity and a preparation method thereof. Background technique

[0002] Lung cancer is one of the most common malignant tumors in the world, and its mortality rate ranks first among all malignant tumors. Lung cancer can be divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), of which 85% belong to non-small cell lung cancer. Most non-small cell lung cancer patients are already in the middle and advanced stages when they are diagnosed, and the 5-year survival rate is very low. With the deepening of scientific research, scientists have discovered that the anaplastic lymphoma kinase (ALK) fusion gene is one of the key genes driving non-small cell lung cancer.

[0003] At present, molecular targeted therapy is the most effective and most widely used treatment method among man...

Examples

Embodiment Construction

[0029] The technical solutions of the present invention will be further described below in conjunction with specific embodiments.

[0030]

[0031] 5-Chloro-N 4 -(2-(isopropylsulfonyl)phenyl)-N 2 The preparation method of -(2-phenylimidazol[1,2-c]pyrimidin-7-yl)pyrimidine-2,4-diamine is shown in the following chemical reaction process.

[0032]

[0033] Step 1, the preparation of 2-phenylpyrimidin [1,2-c] imidazol-7-amine

[0034] Add 4,6-diaminopyrimidine (110.1mg, 1.00mmol) and methanol (5mL) sequentially into a 100mL three-necked flask, stir magnetically to dissolve the raw materials, then add 2-bromoacetophenone (199.0mg, 1.00mmol), Triethylamine (121.4mg, 1.20mmol), heated to 55°C, stopped the reaction after 5h, cooled to 25°C, a light yellow solid precipitated, filtered the filtrate, and isolated a white solid (178.7mg, 85%).

[0035] 1 H NMR (500MHz, DMSO-d 6 ), δ: 9.18(s, 1H), 8.38(s, 1H), 7.86(d, J=7.5Hz, 2H), 7.57(t, 2H), 7.50(t, 1H), 6.50(s, 2H) ,7.70(s,...