5-[(4-chlorophenoxy)methyl]-3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazole Chemical Properties

Boiling point:

223.4±32.0 °C(Predicted)

Density 

1.297±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

1.70±0.39(Predicted)

Appearance

Light yellow to yellow Solid

5-[(4-chlorophenoxy)methyl]-3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazole Usage And Synthesis

Uses

2-(Chloromethyl)quinazoline is used as a reactant in the preparation of carboxyflavones as CysLT1 (LTD4) receptor antagonists.

Synthesis

General procedure for the synthesis of 2-(chloromethyl)quinazoline from 2-chloro-N-(2-formylphenyl)acetamide: 2-chloro-N-(2-formylphenyl)acetamide (0.869 g, 4.40 mmol) was stirred with a methanol solution of 7 N ammonia (4.4 mL, 30.8 mmol) in a sealed tube for 4.5 h at room temperature. The progress of the reaction was monitored by TLC (9:1 hexane/EtOAc) and it was found that a new point with lower Rf value was generated, but a large amount of feedstock remained unreacted. Subsequently, stirring was continued at room temperature for 19.5 hours, during which a white precipitate was formed. Volatiles were removed under reduced pressure to give a beige solid, which was treated with CHCl3. Examination of the soluble fraction of CHCl3 by TLC (7:3 hexane/EtOAc) revealed that the main component was a new point with an Rf value lower than that of the starting material. The CHCl3 solution was placed in a 0°C refrigerator for the weekend. The insoluble material was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on an Analogix IF-280 (Agilent SF10-4g, 100% CHCl3) with the product eluting in fractions 1-10. The product-containing fractions were combined and concentrated under reduced pressure to afford 2-(chloromethyl)quinazoline as a white solid (418 mg, 53.2% yield).1H NMR (300 MHz, CDCl3) δ 9.45 (s, 1H), 8.09-8.04 (m, 1H), 7.99-7.92 (m, 2H), 7.70 (ddd, J = 8.0, 6.9 1.2 Hz, 1H), 4.92 (s, 2H).

References

[1] Patent: US2013/343992, 2013, A1. Location in patent: Paragraph 0302