tert-Butyl 2,4-dichloro-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate

Uses

tert-Butyl 2,4-dichloro-7,8-dihydropyrido[4,3-d]pyrimidine-6(5H)-carboxylate is a tert-butyl ester compound used in the synthesis of tetrahydropyrimidine derivatives as AHR modulators.

Synthesis

2,4-Dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (270 mg, 1.33 mmol) and di-tert-butyl dicarbonate (348 mg, 1.6 mmol) were used as the starting material, and 2,4-dichloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine was dissolved in dichloromethane (30 mL) at 0 °C. Triethylamine (200 mg, 2.0 mmol) was then added and the reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the organic layer was separated by diluting the reaction mixture with dichloromethane (30 mL) and water (30 mL). The aqueous phase was further extracted with dichloromethane (30 mL x 2). All organic layers were combined, washed with brine and dried with anhydrous sodium sulfate. After filtration to remove the desiccant, the solvent was removed by concentration under reduced pressure. The resulting crude product was purified by fast column chromatography using a solvent mixture of hexane and ethyl acetate to afford N-BOC-2,4-dichloro-5,7,8-trihydropyrido[4,3-D]pyrimidine (300 mg, 74% yield). Mass spectrometry analysis (LRMS, M+H+): calculated value 305.17; measured value 305.24.

References

[1] Patent: WO2014/15291, 2014, A1. Location in patent: Page/Page column 172; 173
[2] Journal of Medicinal Chemistry, 2015, vol. 58, # 24, p. 9480 - 9497