2,4-dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine hydrochloride

Uses

2,4-Dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine Hydrochloride acts as a reagent in the preparation of fused aminopyrimidines as glucose uptake inhibitors for treating parasitic and viral infections.

Synthesis

The general procedure for the synthesis of 2,4-dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine hydrochloride using 6-benzyl-2,4-dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine as starting material was as follows: compound (C) (35.0 g, 0.106 mol) prepared in step 2 was dissolved in 1,2-dichloroethane (850 mL ), followed by the addition of triethylamine (14.9 mL, 0.107 mol) and 1-chloroethyl chloroformate (34.1 mL, 0.316 mol). The reaction mixture was stirred under heated reflux conditions for 5 hours. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was cooled, washed sequentially with water and saturated saline and the organic phase was dried with anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=3:1). The purified product was dissolved in methanol (850 mL) and heated to reflux stirring for 1 hour. The reaction process was again confirmed by TLC. After completion of the reaction, it was concentrated to dryness under reduced pressure to afford the target compound (D) (23.5 g, 95% yield).

References

[1] Patent: EP1537879, 2005, A1. Location in patent: Page/Page column 61-62
[2] Patent: EP1547616, 2005, A1. Location in patent: Page/Page column 65-66
[3] Journal of Medicinal Chemistry, 2012, vol. 55, # 24, p. 10958 - 10971