| 主权项 |
1. A process for the preparation of compounds of Formula (I): wherein each R′ is independently selected from substituted C1-C8 alkyl groups or a pharmaceutically acceptable salt thereof; said process comprising the steps of: (a) providing a compound of Formula (III): wherein PG1 is selected from the group consisting of —C(O)—R, —C(O)—OR, —S(O)2—R, —C(O)N(R)2, and —S(O)2N(R)2;each R is independently selected from the group consisting of hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, heterocyclic, aryl, and heteroaryl, each optionally substituted;PG2 is selected from acyl, silyl, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, and a saturated or unsaturated heterocyclic group;alternatively, PG1 and PG2 are tethered together to form a heterocyclic ring; (b) treating the compound of Formula (III) with a deprotonating agent followed by an alkylating agent followed by quaternizing agent to provide a compound of Formula (IV): (c) reacting the compound of Formula (IV) with a sulfur ylide in the presence of a base to yield a compound of Formula (V): (d) reducing and deprotecting the compound of Formula (V) to provide a compound of Formula (VI): (e) protecting the compound of Formula (VI) to yield a compound of Formula (VII): wherein PG is selected from the group consisting of —R, —C(O)—R, —C(O)—OR, —S(O)2—R, —C(O)N(R)2, and —S(O)2N(R)2, wherein R is as previously defined; (f) reacting the compound of Formula (VII) with an oxidizing reagent to yield a compound of Formula (VIII): (g) reacting the compound of Formula (IX): wherein X1 is a leaving group, with wherein R1 is hydrogen or silyl, in the presence of a metallic catalyst or a combination of metallic catalysts to provide a compound of Formula (X): (h) reacting the compound of Formula (VIII) with the compound of Formula (X) under amide formation condition to provide a mixture of compounds of Formulae (XI-a) and (XI-b): (i) treating the mixture of compounds of Formulae (XI-a) and (XI-b) with an acid to yield a compound of Formula (XII): (j) optionally when R1 is a silyl group, treating the compound of Formula (XII) with a base to yield a compound of Formula (XII-a): (k) treating the compound of Formula (XIII)wherein X2 is a leaving group, with a halogenating reagent to yield a compound of Formula (XIV):wherein X3 is halogen;
(l) reacting the compound of Formula (VIII) with the compound of Formula (XIV) in the presence of an base to provide a compound of Formula (XV): (m) treating the compound of formula (XV) with an ammonium salt to provide a compound of Formula (XVI): (n) reacting the compound of Formula (XII-a) with the compound of Formula (XVI) in the presence of a metallic catalyst to provide a compound of Formula (XVII): (o) deprotecting the compound of Formula (XVII) to provide a compound of Formula (XVIII): (p) reacting the compound of Formula (XVIII) with under amide formation condition to provide a compound of Formula (I): |
