5-Fluoro-2-methoxy-4(3H)-pyrimidinone

Off-White Solid

In the dried reaction kettle, cold brine was jacketed, the temperature was lowered to below 25 C, and 700 kg of toluene was charged.Open the feed hole and put 224kg of solid sodium methoxide, close the feed hole, open the stirring, and open the empty valve.420 kg of ethyl formate was pumped into the ethyl formate measuring tank, the reaction pot was jacketed with cold brine, cooled to an internal temperature of 10 to 15 C, and ethyl formate was slowly added dropwise to control the internal temperature of 10 to 20 C, about 3-4 The hour is finished.200 kg of methyl fluoroacetate was pumped into the methyl fluoroacetate metering tank, and the internal temperature was cooled to 8-15 C with cold brine, and methyl fluoroacetate was added dropwise. The internal temperature should not exceed 25 C during the dropwise addition. After completion of the dropwise addition, the internal temperature was controlled at about 40 C. for about 20 hours until the reaction was completed. Cyclic reaction:The reaction solution was cooled to an internal temperature of 20 C, and 390 kg of a sodium methoxide methanol solution and 400 kg of O-methylisourea sulfate were slowly added in sequence under stirring, and the stirring was continued, and the internal temperature was maintained at about 40 degrees for about 6 hours until the reaction was completed. Transfer the reaction solution to a dissolving layered pot, add 500 kg of water and 60 kg of hydrochloric acid, dilute hydrochloric acid, and then transfer the lower aqueous layer to the primary acidification pot to dissolve the pot. While stirring, slowly add hydrochloric acid and keep the internal temperature at 35 C. Next, neutralize to a pH of 5 to 6, and concentrate under reduced pressure until the effluent is significantly reduced, then add 1000 kg of water and dilute hydrochloric acid, adjust the pH to 2 to 3, and suction filter to obtain a crude product. The crude product is dissolved in 1000 kg of water, stirred and heated to an internal temperature of 90 to 100 C, and after being held for 30 minutes, it is cooled to an internal temperature of 40 C.After centrifugation, 5-methoxyfluorouracil (221.7kg, yield 81.63%) was obtained as a yellow cyclic compound500 g of methanol was placed in a constant-temperature reaction bath, and hydrogen chloride gas was introduced until the methanol increased weight to 543 g-556 g to stop aeration. The prepared methanol solution of hydrogen chloride was placed in a refrigerator for use.In a dry and clean 500 mL four-neck flask, 250 g of hydrochloric acid in methanol was added, and 50 g of 90 kg of the yellow cyclic compound obtained above was added, and 198 kg of concentrated hydrochloric acid was added, and reacted at a temperature of 55 C. for 3 hours until the reaction was completed. After the reaction is completed, the solution is cooled to an internal temperature of 5 to 15 C with cold brine. The feed liquid is transferred to a centrifuge, centrifuged, washed with water to pH 5 to 6, and dried to obtain crude 5-fluorouracil.(65.24 kg, yield 80.3%, HPLC purity 98.45%).The 14.4g type IV compounds add 29 ml of toluene and 15.2g in triethylamine, heating to 50-80°C, dropwise 18.4g phosphorus oxychloride, the drop finishes, preserving heat and stirring reaction 5-7 hours, cooling to room temperature, adding water, separating, collecting the organic phase, organic phase is concentrated under reduced pressure, compound III namely type (strawcoloured liquid) 15.4g, molar yield is 95.0percent, HPLC purity of 95.8percent.43b2-Methoxy-5-fluorouracil (43a, 1.04g, 7.21 mmol) and N, N-dimethylaniline (1.80 mL) were heated in POCI3 at 11O0C for 90 minutes. After cooling, the reaction was added carefully to ice. The product was extracted with diethylether. The ether layer was washed with sequentially with 2N HCI, water, and brine followed by drying (MgSO4). The ether was carefully removed under reduced pressure to give 43b as a volatile liquid (0.39g, 34percent) which was used without further purification. Rf = 0.26 (10percent EtOAc/hexane). 1H NMR (400MHz, DMSO-d6): delta 3.91 (s, 3H), 8.79 (s, 1 H)

Molecular Weight:144.10
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:144.03350557
Monoisotopic Mass:144.03350557
Topological Polar Surface Area:50.7
Heavy Atom Count:10
Complexity:222
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes