摘要 |
The invention in one embodiment is directed to a method of preparing a compound of formula (1), or a pharmaceutically acceptable salt thereof, wherein R1 and R2 are each independently chosen from hydrogen, (C1-C6)alkyl, and cycloalkyl, R is -NR3R4, where R3 and R4 are each independently chosen from hydrogen, and (C1-C4)alkyl; and n ranges from 1-4, comprising: (a) reacting a C1-C12 alkyl nitrate with a compound of formula (2), or a salt thereof, in the presence of an acid at a concentration greater than 70% weight of acid / weight of solution, the acid being selected from the group consisting of sulfuric acid, and R5-SO3H wherein R5 is C1-C4 alkyl optionally substituted with one or more halogen, or R5 is C6-C10 aryl optionally substituted with one or more C1-C4 alkyl or halogen, to produce a reaction mixture containing a compound of formula (3) or a salt thereof; (b) reducing the compound of formula (3) or a salt thereof to form a compound of formula (4) or a salt thereof; (c) acylating the compound of formula (4) to form a compound of formula (1), and (d) optionally forming a pharmaceutically acceptable salt of the compound of formula (1).
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