155-12-4

基本信息
2-氯-5-氟-4-嘧啶酮
2-氯-4-羥基-5-氟嘧啶
2-氯-5-氟-4-羥基嘧啶
2-氯-5-氟嘧啶-4(3H)-酮
2-氯-5-氟-3H-嘧啶-4-酮
2-氯-4-羥基-5-氟嘧啶 1G
4-(1H)-嘧啶酮,2-氯-5-氟-
2-氯-4-羥基-5-氟嘧啶(CAS號(hào):155-12-4)
2-Chloro-5-fluoro-pyrimidin-4-ol
2-Chloro-5-fluoro-4-pyrimidinone
2-Chloro-5-fluoropyriMidin-4(3H)-one
2-Chloro-5-fluoro-3H-pyriMidin-4-one
2-chloro-5-fluoro-1H-pyrimidin-6-one
2-Chloro-5-fluoro-1H-pyriMidine-6-one
2-Chloro-4-hydroxy-5-fluoropyrimidine
2-chloro-5-fluoro-4-hydroxypyrimidine
4(3H)-Pyrimidinone, 2-chloro-5-fluoro-
物理化學(xué)性質(zhì)
制備方法

2927-71-1

155-12-4
以2,4-二氯-5-氟嘧啶為原料合成2-氯-5-氟嘧啶-4(3H)-酮的一般步驟如下:在氮?dú)獗Wo(hù)下,將二甲基苯胺(195 mL,1.54 mol)加入到5-氟尿嘧啶(99.73 g,0.77 mol)與磷酰氯(215 mL,2.31 mol)形成的漿液中,反應(yīng)溫度維持在95℃。反應(yīng)混合物在該溫度下攪拌3.5小時(shí)后,冷卻至室溫,隨后緩慢倒入攪拌的冰(200 g)和6M鹽酸(200 mL)的混合物中。所得漿液用二氯甲烷(2×400 mL)萃取,合并的有機(jī)相用去離子水(4×275 mL)洗滌,經(jīng)無水硫酸鎂干燥后減壓濃縮,得到5-氟-2,4-二氯嘧啶111.77 g(收率87%,HPLC測(cè)定純度為98.1% AUC),呈琥珀色油狀。接著,在0℃下,將1.34 L的1M氫氧化鈉溶液緩慢加入到5-氟-2,4-二氯嘧啶(111.77 g,0.67 mol)的四氫呋喃(377 mL)溶液中。反應(yīng)混合物在室溫下攪拌約30分鐘后,用1.0M鹽酸緩慢調(diào)節(jié)pH至6。水相用乙酸乙酯(440 mL)萃取以去除雜質(zhì),隨后用1.0M鹽酸調(diào)節(jié)pH至1。酸性水相用乙酸乙酯(4×555 mL)萃取,合并的有機(jī)相用鹽水(111 mL)洗滌,經(jīng)無水硫酸鎂干燥后減壓濃縮,得到2-氯-5-氟-3H-嘧啶-4-酮88.35 g(收率89%,HPLC測(cè)定純度為99% AUC),為灰白色粉末。
參考文獻(xiàn):
[1] Patent: EP1506967, 2005, A1. Location in patent: Page/Page column 67
[2] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 18, p. 4984 - 4995
[3] Patent: US2007/66636, 2007, A1. Location in patent: Page/Page column 19; 20
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 2, p. 510 - 524
[5] Patent: US2007/60529, 2007, A1. Location in patent: Page/Page column 14