[Synthesis]
(A) Synthesis of 2-chloro-5-(cyclopropylmethoxy)pyrimidine: Cyclopropylmethanol (276 mg, 3.0 mmol), 2-chloropyrimidin-5-ol (500 mg, 3.8 mmol) and triphenylphosphine (1.51 g, 5.8 mmol) were dissolved in anhydrous toluene (20 mL) under nitrogen protection. Subsequently, diisopropyl azodicarboxylate (DIAD, 1.9 M in toluene, 3 mL, 5.7 mmol) was slowly added dropwise under ice bath cooling. After the dropwise addition was completed, the ice bath was removed and the reaction mixture was stirred at room temperature overnight (~12 hours). Upon completion of the reaction, the solvent was removed by distillation under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate, gradient elution) to afford the target compound 2-chloro-5-(cyclopropylmethoxy)pyrimidine (659 mg, yield: 85%). The structure of the product was confirmed by 1H NMR (300 MHz, DMSO-d6): δ 0.21-0.49 (2H, m, cyclopropyl-H), 0.49-0.69 (2H, m, cyclopropyl-H), 1.07-1.46 (1H, m, cyclopropyl-H), 4.00 (2H, d, J = 7.2 Hz, OCH2), 8.53 (2H, s Pyrimidine-H). |