4-Chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine

Uses

4-chloro-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine is a useful reactant for the synthesis of thieno[2,3-d]pyrimidines and furo[2,3-d]pyrimidines derivatives, for the use as c-Met inhibitiors as a potential antitumor agents.

Synthesis

GENERAL METHOD: Different thieno[2,3-d]pyrimidin-4-one derivatives (6a-d or f-i) (1 eq.) were mixed with phosphorochloridic acid chloride (2.9 mL/mmol eq.) and heated to reflux for 8 hours. Upon completion of the reaction, the reaction mixture was cooled in an ice bath and neutralized by slow addition of saturated aqueous sodium bicarbonate solution. Subsequently, the reaction mixture was extracted with ethyl acetate (15 mL/millimolar equivalent), the organic layer was separated, dried with anhydrous magnesium sulfate and concentrated under reduced pressure. The crude product was purified by fast column chromatography with the eluent being n-hexane-ethyl acetate (initial ratio 100:0 v/v), which was gradually adjusted to n-hexane-ethyl acetate (85:15 v/v), unless otherwise stated.

References

[1] Chemical and Pharmaceutical Bulletin, 1982, vol. 30, # 1, p. 326 - 332
[2] European Journal of Medicinal Chemistry, 2016, vol. 123, p. 31 - 47
[3] Synthesis, 2001, # 14, p. 2119 - 2123