Pyrimidine derivative, synthesis method and applications thereof

A technology of pyrimidine derivatives and pyrimidine, which is applied in the structure of pyrimidine derivatives and the field of preparation thereof, can solve the problems of drug resistance, patient resistance and the like, and achieves the effects of easy operation and simple preparation process.

CN111171033AActive Publication Date: 2020-05-19TIANJIN UNIV
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2020-05-19

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Abstract

The invention discloses a pyrimidine derivative, a synthesis method and applications thereof. The synthesis method comprises the following steps: obtaining an arylamine compound 2-phenylpyrimidine [1,2-c]imidazole-7-amine, and then carrying out a catalytic coupling reaction on the arylamine compound 2-phenylpyrimidine [1,2-c]imidazole-7-amine and 2,5-dichloro-N-(2-(isopropylsulfonyl)phenyl)pyrimidine-4-amine to obtain the pyrimidine derivative. The preparation method has the advantages that the preparation process is simple and easy to operate. The prepared product has ALK inhibitory activityand can be used for preparing an ALK inhibitor.
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Description

Technical field

[0001] The invention belongs to the field of medicinal chemistry, and more specifically, relates to the 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 patients with non-small cell lung cancer are already in the advanced stage when they are diagnosed, and the 5-year survival rate is very low. With the deepening of scientific research, scientists have discovered that 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 therapeutic method among many methods for...

Examples

Embodiment Construction

[0029] The technical solution 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-phenylimidazole[1,2-c]pyrimidin-7-yl)pyrimidine-2,4-diamine is shown in the following chemical reaction process.

[0032]

[0033] Step 1, Preparation of 2-phenylpyrimidine [1,2-c]imidazole-7-amine

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

[0035] 1 H NMR(500MHz, DMSO-d 6 ), δ: 9.18 (s, 1H), 8.38 (s, 1H), 7.86 (d, J = 7.5 Hz, 2H), 7.57 (t, 2H), 7.50 (t, 1H), 6.50 (s, 2H) ,7.7...