ChemicalBook CAS DataBase List 2-Chloropyrimidine-5-carbonitrile

2-Chloropyrimidine-5-carbonitrile synthesis

7synthesis methods

Product Name:2-Chloropyrimidine-5-carbonitrile
CAS Number:1753-50-0
Molecular formula:C5H2ClN3
Molecular Weight:139.54

To a stirring solution of 2-aminopyrimidine-5 -carbonitrile (1.0 g, 8.33 mmol) in CH3CN (15 ml) at room temperature under Argon added copper (II) chloride (1.679 g, 12.5 mmol) and test-butyl nitrite (1.288 g, 12.5 mmol). The reaction mixture was placed under Argon in a preheated oil bath (60 ℃). The reaction mixture was cooled to room temperature, and 20 ml of ether was added. The resulting insoluble material was filtered, and the filtrate was concentrated. The crude product was dissolved in a small amount of DCM (~2 ml) and loaded onto a 40 g ISCO silica gel column which was eluted with a 20 min gradient from 0% to 100% EtOAc/Hexanes. 723 mg (61%) of 2-chloropyrimidine-5-carbonitrile was obtained as a tan solid.

1753-48-6
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$31.00/1g

1753-50-0
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$18.00/250mg

Yield:1753-50-0 72%

Reaction Conditions:

Stage #1:2-aminopyrimidine-5-carbonitrile with tert.-butylnitrite in acetonitrile at 20; for 1 h;Inert atmosphere;
Stage #2: with copper dichloride in acetonitrile at 60; for 24 h;

Steps:

3 (3) synthesis of 2-chloropyrimidine-5-carbonitrile
A 500 mL two-necked flask was added with 5-bromopyrimidin-2-amine (5.18 g, 30 mmol), Zn(CN)₂(2.11 g, 18 mmol), Pd(PPh₃)₄(3.46 g, 3 mmol), Zinc (0.045 g, 1.5 mmol), and Zn(OAc)₂(0.33 g, 1.5 mmol), equipped with a magnetic stirring bar, an addition funnel, and a condensing tube, and charged with argon after evacuation. Dry DMF (300 mL) was injected with a syringe, heated at 120° C. for 24 hours, allowed to cool down to RT, and poured into 1000 mL water. The white powder was precipitated, filtered, and washed with methanol, giving a white powder formed 2-aminopyrimidine-5-carbonitrile. Then, a 100 mL two-necked flask was added with 2-aminopyrimidine-5-carbonitrile (3.6 g, 30 mmol), tert-butyl nitrite (BuNO) (5.35 mL, 43 mmol), equipped with a magnetic stirring bar, an addition funnel, and a condensing tube, and charged with argon after evacuation. Acetonitrile (60 mL) was firstly injected with a syringe, stirred at RT for 1 hour, and then a solid CuCl₂was added, heated at 60° C. for 24 hours. After cool down to RT, 20 mL diethyl ether was added and filtered. After the filtrate was subjected to rotary concentration to remove excess solvent, the solid was purified by column chromatography (SiO₂, Dichloromethane/Hexane=1/1), giving a white solid (3 g, 22 mmol, 72%). ¹H NMR (400 MHz, CDCl₃) δ ppm 8.90 (s, 2H). The preparation process is shown below.

References:

AU OPTRONICS CORPORATION;HU, Hung-Chieh;CHEN, Chung-Chia;LEE, Meng-Ting;HO, Yu-Yi;LI, Shu-Wei;WONG, Ken-Tsung;PAN, Kuan-Chung;SHIU, Yi-Jiun;TSAI, Wei-Lung;WU, Chung-Chih US2017/170419, 2017, A1 Location in patent:Paragraph 0041

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