ETHYL 4-CHLORO-5-METHYLTHIENO[2,3-D]PYRIMIDINE-6-CARBOXYLATE

ETHYL 4-CHLORO-5-METHYLTHIENO[2,3-D]PYRIMIDINE-6-CARBOXYLATE Property

Melting point:

114-115 °C(Solv: chloroform (67-66-3); hexane (110-54-3))

Boiling point:

374.4±37.0 °C(Predicted)

Density 

1.409

storage temp. 

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

pka

-0.01±0.40(Predicted)

Safety

HS Code 

2933599590

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H319Causes serious eye irritation

Precautionary statements

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

ETHYL 4-CHLORO-5-METHYLTHIENO[2,3-D]PYRIMIDINE-6-CARBOXYLATE Chemical Properties,Usage,Production

Synthesis

Ethyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-D]-pyrimidine-6-carboxylate (425 mg, 1.783 mmol) was used as a starting material, and after dissolution in toluene (8 mL), N,N-diisopropylethylamine (DIPEA, 248 μL, 1.426 mmol, 0.8 eq.) and phosphorus oxychloride (POCl3, 199 μ L, 2.14 mmol, 1.2 equiv). The reaction mixture was heated to reflux in an oil bath at 120-125°C for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently slowly poured into a mixed system of ice-cooled saturated aqueous sodium bicarbonate (20 mL) and ethyl acetate (EtOAc, 50 mL) with rapid stirring to thoroughly quench the excess of phosphorous trichloride. The organic and aqueous phases were separated and the organic phase was washed once more with saturated aqueous sodium bicarbonate (20 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to afford ethyl 4-chloro-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (25B) as a yellow solid (432 mg, 94% yield).

References

[1] Patent: WO2005/42537, 2005, A1. Location in patent: Page/Page column 57
[2] European Journal of Medicinal Chemistry, 2016, vol. 115, p. 148 - 160
[3] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 9, p. 1663 - 1669
[4] Pharmazie, 1993, vol. 48, # 3, p. 192 - 194
[5] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1985, vol. 21, # 7, p. 767 - 770