| 主权项 |
1. A method of preparing a compound of Formula I:or pharmaceutically acceptable salt thereof wherein:
Z1 is O or S; Each of Y1, Y2 and Y3 is independently a bond, —S—, —O—, or —NR100—,
R100 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, heteroaryl, aryl(C1-6 alkyl), C3-8 cycloaliphatic, or a saturated, partially unsaturated, or fully unsaturated 3-8 membered heterocyclic ring having up to 3 heteroatoms independently selected from N, O, or S; and Each of R1, R2 and R3 is independently -L-R5, wherein
Each L is independently a bond, —(CH2)m—, —(CH2)m(CHR6)p—, —(CH2)m—(CR6R7)p—, or —(C(R8)2)mC(O)O—,Each of R6 and R7 is independently selected from hydrogen, halogen, —OH, —N(R8)2, or −OR8,Each R8 is independently hydrogen or C1-6 alkyl,Each m is independently 0-3,Each p is independently 0-3,Each R5 is independently hydrogen, —O−, —OH, alkoxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —(C(R8)2)mC(O)OR8, aryl, aryl(C1-6 alkyl), C3-8 cycloaliphatic, heteroaryl, a saturated or partially unsaturated 3-8 membered heterocyclic ring having up to 3 heteroatoms independently selected from N, O, or S, an optionally substituted amine, an optionally substituted N-linked amino acid, an optionally substituted N-amino acid ester derivative, orwherein each R4 is independently absent or hydrogen, and n is 0 or 1, and wherein the alkyl, alkenyl, alkynyl, aryl, aryl-(C1-6 alkyl), cycloaliphatic, heteroaryl, or heterocyclic ring groups are each optionally substituted with 1-3 groups independently selected from halo, —OH, —CN, azido, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkoxy, an optionally substituted heterocyclic base, or an optionally substituted heterocyclic base with a protected amino group;
comprising the step of: i) reacting a compound of Formula A with a compound of Formula Bwherein X is a leaving group, in the presence of an acid or a metal salt, to generate the compound of Formula I. |
