| 主权项 |
1. A process for preparing a compound of the formulaor a pharmaceutically acceptable salt thereof; wherein
Ar1 is optionally substituted aryl or optionally substituted heteroaryl; R1 is hydrogen, alkyl, arylalkyl or a pro-drug forming group; R2 is selected from the group consisting of optionally substituted alkyl and optionally substituted cycloalkyl; R12 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl or heteroarylalkyl, each of which is optionally substituted; R3 is optionally substituted alkyl; R4 is optionally substituted alkyl or optionally substituted cycloalkyl; R5 and R6 are each independently selected from the group consisting of optionally substituted alkyl and optionally substituted cycloalkyl; R7 is optionally substituted alkyl; and n is 1, 2, 3, or 4; wherein the process comprises the step of treating a compound of formula A with triethylsilyl chloride and imidazole in an aprotic solvent, where R8 is C1-C6 unbranched alkylorthe step of treating a compound of formula B with a base and a compound of the formula ClCH2OC(O)R2 in an aprotic solvent at a temperature from about −78° C. to about 0° C.; wherein the molar ratio of the compound of the formula ClCH2OC(O)R2 to the compound of formula B from about 1 to about 1.5, where R8 is C1-C6 unbranched alkylorthe steps of a) preparing a compound of formula (E1), where X1 is a leaving group, from a compound of formula Eand b) treating a compound of formula C under reducing conditions in the presence of the compound of formula E1, where R8 is C1-C6 unbranched alkylorthe step of contacting compound D with an alcohol, R12OH, where R12 is alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl or heteroarylalkyl, each of which is optionally substituted; and a transesterification catalyst selected from the group consisting of (R13)8Sn4O2(NCS)4, (R13)2Sn(OAc)2, (R13)2SnO, (R13)2SnCl2, (R13)2SnS, (R13)3SnOH, and (R13)3SnOSn(R13)3, where R13 is independently selected from alkyl, arylalkyl, aryl, or cycloalkyl, each of which is optionally substituted;orthe step of treating the compound AF with a metal hydroxide or a metal carbonate;orthe step of treating a compound of formula BG with an acylating agent of formula R4C(O)X2, where X2 is a leaving grouporthe steps of c) forming an active ester intermediate from a compound of formula AHand d) reacting the active ester intermediate with a compound of the formula I;orone or more combinations thereof. |
