5-(CHLOROMETHYL)-2-METHOXYPYRIDINE Chemical Properties

Boiling point:

236.1±25.0℃ (760 Torr)

Density 

1.173±0.06 g/cm3 (20 ºC 760 Torr)

Flash point:

96.6±23.2℃

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

pka

2.62±0.10(Predicted)

Appearance

Colorless to light yellow Liquid

5-(CHLOROMETHYL)-2-METHOXYPYRIDINE Usage And Synthesis

Uses

5-(Chloromethyl)-2-methoxypyridine is used in preparation of pyrazolopyridine compounds as RET kinase inhibitor for treatment of RET-related diseases.

Synthesis

(6-Methoxypyridin-3-yl)methanol (2) (537.8 g, 3.86 mol) obtained in Preparation Example 1 was dissolved in dimethylformamide (1.6 L), cooled in an ice bath under nitrogen protection, and thionyl chloride (310 mL, 4.25 mol) was added slowly and dropwise over a period of 1.3 hours. After the dropwise addition, the reaction mixture was continued to be stirred in an ice bath for 1 hour. Subsequently, toluene (5.4 L) and 2N aqueous sodium hydroxide solution (5.4 L) were sequentially added to the reaction mixture at a temperature not exceeding 23 °C. After stirring for about 10 minutes, the aqueous layer was separated and the organic layer was washed with water (2.7 L). The organic layer was concentrated to dryness under reduced pressure, and toluene (1.0 L) was added to the residue for azeotropic distillation, resulting in 618.8 g of the target product, 5-chloromethyl-2-methoxypyridine (3), as a light yellow oil (556.3 g, 91.4% yield). The structure of the product was confirmed by 1H-NMR (CDCl3): δ (ppm) 8.15 (1H, d, J=2.4 Hz), 7.63 (1H, dd, J=2.4 Hz, 8.4 Hz), 6.75 (1H, d, J=8.4 Hz), 4.55 (2H, s), 3.94 (3H, s).

References

[1] Patent: WO2016/33445, 2016, A1. Location in patent: Paragraph 0259
[2] Tetrahedron, 2014, vol. 70, # 40, p. 7207 - 7220
[3] Patent: US2006/235225, 2006, A1. Location in patent: Page/Page column 4
[4] Patent: US2007/49632, 2007, A1. Location in patent: Page/Page column 38
[5] Patent: US2011/224225, 2011, A1. Location in patent: Page/Page column 23

5-(CHLOROMETHYL)-2-METHOXYPYRIDINE(101990-70-9)Related Product Information

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• 5-(CHLOROMETHYL)-2-ETHOXYPYRIDINE
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• 5-(CHLOROMETHYL)-2-METHOXYPYRIDINE HYDROCHLORIDE