34171-37-4

105-54-4

17356-08-0

109-94-4

34171-37-4

Step D75: Synthesis of 5-ethyl-2-thio-2,3-dihydro-4(1H)-pyrimidinone 1. To a suspension of potassium tert-butanolate (12.08 g, 108 mmol) in THF (40 mL) under nitrogen protection was slowly added dropwise a mixed solution of ethyl butyrate (5.69 mL, 43.0 mmol) and ethyl formate (6.93 mL, 86 mmol) in ether (40.0 mL). 2. The reaction mixture was stirred at room temperature for 3 hours. 3. Upon completion of the reaction, the solvent was removed under reduced pressure to give an oily residue. 4. The residue was dissolved in isopropanol (350 mL) and thiourea (6.55 g, 86 mmol) was added. 5. The mixture was heated to reflux and stirred overnight. 6. At the end of the reaction, the reaction solution was concentrated under vacuum to give a solid product. 7. The solid product was dissolved in water and the pH was adjusted to 4 with acetic acid (AcOH). 8. 8. The aqueous phase was extracted with dichloromethane (DCM) and the organic layers were combined. 9. The organic layer was dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to give 5-ethyl-2-thiouracil (5.5 g, 82% yield) as a pink solid.