Patent ID: 6121437
Filing Date: 2000-09-19
Classification: C07H,Y02P

Abstract:
A method for the preparation of an oligomeric compound comprising a moiety of Formula X: ##STR48## wherein: W is selected independently from O and S;X is selected independently from O and S;Y is selected independently from O and NR.sup.2 ;Z is selected independently from a single bond, O, and NR.sup.2 ;R.sup.1, at each occurrence, is selected independently from C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, CN, NO.sub.2, Cl, Br, F, I, CF.sub.3, OR.sup.4, NR.sup.5a R.sup.5b, and phenyl;alternatively, two R.sup.1 groups, when on adjacent carbons of the phenyl ring, join to form a napthyl ring that includes said phenyl ring;R.sup.2, at each occurrence, is selected independently from H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, and phenyl;R.sup.3, at each occurrence, is selected independently from hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, and phenyl;R.sup.4 is selected independently from C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, and phenyl;R.sup.5a and R.sup.5b, at each occurrence, are selected independently from C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, and phenyl;n is selected independently from 0, 1, 2, and 3; andm is selected independently from 0, 1, 2, and 3;the method comprising:(a) providing a compound of Formula II: ##STR49## wherein: R.sup.6, at each occurrence, is selected independently from H, a hydroxyl protecting group, and a linker connected to a solid support;R.sup.7, at each occurrence, is indepedently H, hydroxyl, C.sub.1-20 alkyl, C.sub.3-20 alkenyl, C.sub.2-20 alkynyl, halogen, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, dilulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, or one of formula XII or XIII: ##STR50## wherein E is selected from C.sub.1-10 alkyl, N(R.sup.15)(R.sup.17) and N.dbd.C(R.sup.15)(R.sup.17);R.sup.15 and R.sup.17 are independently selected from H, C.sub.1-10 alkyl, dialkylaminoalkyl, a nitrogen protecting group, a tethered or untethered conjugate group, a linker to a solid support, or alternatively R.sup.15 and R.sup.17, together, are joined in a nitrogen protecting group or a ring structure that can include at least one additional heteroatom selected from N and O;q.sup.1 is from 1 to 10;q.sup.2 is from 1 to 10;q.sup.3 is 0 or 1;R.sup.16 is OR.sup.18, SR.sup.18, or N(R.sup.18).sub.2 ;R.sup.18 is selected independently from H, C.sub.1 -C.sub.8 alkyl, C.sub.1 -C.sub.8 haloalkyl, C(.dbd.NH)N(H)R.sup.19, C(.dbd.O)N(H)R.sup.19 and OC(.dbd.O)N(H)R.sup.19 ;R.sup.19 is H or C.sub.1 -C.sub.8 alkyl;L.sub.1, L.sub.2 and L.sub.3 comprise a ring system having from about 4 to about 7 carbon atoms or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms wherein said hetero atoms are selected from oxygen, nitrogen and sulfur and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic;L.sub.4 is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(R.sup.15)(R.sup.17) OR.sup.15, halo, SR.sup.15 or CN; andq.sup.4 is, 0, 1 or 2;R.sup.8 is selected independently from NR.sup.8a R.sup.8b, and a 5-6 membered heterocyclic system containing 1-4 heteroatoms selected independently from N, O, and S;R.sup.8a and R.sup.8b, at each occurrence, are selected independently from C.sub.1-10 alkyl and C.sub.3-7 cycloalkyl;X.sup.1 is selected independently from O and S;B, at each occurrence, is independently selected from a protected or unprotected naturally occurring nucleobase, and a protected or unprotected non-naturally occurring nucleobase;q is selected independently from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10;p is an integer selected independently from 0 to about 50;Q, at each occurrence, is selected independently from OH, SH, and ##STR51## (b) reacting the compound of Formula II with a compound of Formula III: ##STR52## wherein R.sup.10 is selected independently from a hydroxyl protecting group, and a linker connected to a solid support;with the proviso that R.sup.6 and R.sup.10 are not both simultaneously a linker connected to a solid support; andp' is an integer selected independently from 0 to about 50; to form the oligomeric compound.