3-Amino-5-methylpyridine-2-carbonitrile Chemical Properties

Boiling point:

370.3±42.0 °C(Predicted)

Density 

1.18

storage temp. 

2-8°C(protect from light)

form 

crystal

pka

0.91±0.20(Predicted)

color 

brown

Safety Information

Risk Statements 

25

Safety Statements 

45

HS Code 

2933399990

3-Amino-5-methylpyridine-2-carbonitrile Usage And Synthesis

Uses

3-Amino-2-cyano-5-methylpyridine is a versatile reactant used in the preparation of new series of orally bioavailable chemokine receptor 9 (CCR9) antagonists with potential use for treatment of inflammatory bowel disease.

Synthesis

Under argon protection, 1.0 g (7 mmol, 1 eq.) of 2-chloro-5-methylpyridin-3-amine was dissolved in 15 mL of anhydrous N,N-dimethylformamide (DMF) in a 20 mL reaction vial. Subsequently, 821 mg (7 mmol, 1 equiv) of zinc cyanide (Zn(CN)2) was added. After degassing the reaction system for 10 min, 405 mg (0.35 mmol, 0.05 eq.) of tetrakis(triphenylphosphine)palladium(0) (Pd(PPh3)4) was added. The reaction mixture was heated to 105 °C and the reaction was stirred at this temperature for 20 hours. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: ethyl acetate/petroleum ether, 2/8, v/v) to afford the white solid target product 3-amino-2-cyano-5-methylpyridine in 65% yield. The melting point of the product was 154 °C. Infrared spectrum (diamond ATR, cm^-1) ν: 3404, 2216, 1600, 1465, 1339, 1230, 858, 739; 1H NMR (400 MHz, CDCl3) δ: 2.34 (s, 3H, CH3), 4.37 (br s, 2H, NH2), 6.93 (d, 1H, J = 2.4 Hz. Harom), 7.93 (d, 1H, J = 2.4 Hz, Harom); 13C NMR (101 MHz, CDCl3) δ: 28.7 (CH3), 114.9 (CH), 116.3 (CN), 122.6 (CH), 138.6 (Cq), 142.2 (CH), 146.3 (Cq).

References

[1] Patent: US2015/203489, 2015, A1. Location in patent: Paragraph 0660; 0661