Using furochloric acid, guanidine nitrate as raw materials, through cyclization, decarboxylation, dechlorination. Methanol solution with sodium methanol and guanidine nitrate were added and filtered at 40-45℃ for 30min to obtain guanidine free methanol solution.

1. Add the methanol solution into the reaction tank, and within 30 minutes at 95℃, add furochloric acid-methanol solution, hold the temperature at 60±1℃ for 40 minutes, then vacuum distillation, steam out the methanol to a certain amount, then stop distillation, add water to dissolve the reactants, acidified at 30-35℃ with 30% hydrochloric acid to pH=1, wash with filtration, and dry at 95℃. Coarse ring compound is obtained.

The crude annulus was placed in a sublimator and decarboxylated at 150-300℃ to obtain 2-amino-5-chloridine. The yield of cyclization and decarboxylation is about 67.5%. Isopropyl alcohol, caustic soda water, zinc mud, (60% zinc hydroxide), 2-amino-5-chlorpyrimidine and zinc powder were added to the reaction tank. After reflux for 8h at 77-80℃, the low boiling point distillate was recovered first, and isopropyl alcohol was recovered at 77-100℃. Cool to 77-85℃. Wash cake in hot water. The filtrate and part of the lotion were combined, granular caustic soda was added, and alkali chromatography was performed at 50℃ for 1h. The formaldehyde ester was extracted below 70℃, and the glue was separated. pH=7.5-8 was adjusted with hydrochloric acid, and then the oil was separated. Then the formaldehyde ester was recovered and dihydropyran was precipitated. The finished product is dried at 40-50℃.

2. Reaction of guanidine hydrochloride with proparynaldehyde. Add 90ml concentrated hydrochloric acid to a 300ml three-way flask equipped with a thermometer, drip funnel and agitator, and cool the outside with an ice salt bath. Under stirring condition, 27g guanidine hydrochloride with purity of about 80% is added below 10℃. After carbon dioxide is released, it is cooled to 0℃, and 11.1g crude propargyle (8.7g for folded pure products) is added. When it is added, heat is released, and the reaction temperature rises with it, but it should not exceed 20℃. After the exothermic stop of the reaction, it was placed overnight at room temperature, and then the reaction liquid was moved into the distillation flask, which was decompressed and evaporated and concentrated at about 35℃. After cooling, the product dihydropyran was precipitated by adding 60ml30% sodium hydroxide solution. The substance was extracted with 1500ml benzene at 60-70℃. The benzene solution was cooled and dried with calcium chloride. Distillation removes benzene and produces a product.

dihydropyran https://www.clentpharma.com/3-4-dihydropyran.html