Preparation method of avanafil

• Main Authors: ZHANG ZHAOZHEN, YANG QINGKUN, ZHANG LEILEI, WU KE, ZHOU XUEWEN, LI BAOYONG, ZHOU XIANGUO, DONG TINGHUA, LI YAPENG
• Format: Patent
• Language: English
• Published: 22.04.2015
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention discloses a preparation method of avanafil. The method comprises the steps: carrying out amino protective reaction for cytosine (compound 1) which is used as a starting raw material and di-tert-butyl dicarbonate ester to obtain an intermediate I; enabling the intermediate I to firstly react with hexamethyl-disilazane and then to have friedel-crafts reaction with ethyl chloroformate in the existence of aluminum trichloride to obtain an intermediate II; preparing an intermediate III by virtue of substitution reaction between the intermediate II and 4-bromomethyl-2-chlorine-1-metoxybenzene; facilitating the reaction between the intermediate III and sulfonyl chloride to generate activated ester, and then enabling the activated ester to have condensation reaction with L-prolinol to obtain an intermediate IV, and carrying out the hydrolysis reaction for the intermediate IV to obtain an intermediate V; enabling the intermediate V to firstly react with CDI and then to have acylation reaction with 2-pyrimidinemethanamine oxalate to obtain avanafil. According to the method, raw materials for the reaction in each step are simple and easy to obtain, the operation is simple, the yield is high, the cost is low, and the industrialized production is easy to realize.