Patent ID: 6465628
Filing Date: 2002-10-15
Classification: C07H,Y02P

Abstract:
A synthetic method comprising:a) providing a sample containing a plurality of oligomers of the Formula I: â€ƒwherein: R1 is H or a hydroxyl protecting group, B is a naturally occurring or non-naturally occurring nucleobase that is optionally protected at one or more exocyclic hydroxyl or amino groups; R2 has the Formula III or IV: â€ƒwherein E is C1-C10 alkyl, N(Q1)(Q2) or N&boxH;C(Q1)(Q2); each Q1 and Q2 is, independently, H, C1-C10 alkyl, dialkylaminoalkylenyl, a nitrogen protecting group, or a linker to a solid support, or Q1 and Q2, together, are joined in a nitrogen protecting group or a ring structure that can include at least one heteroatom selected from the group consisting of N and O; A is H, C1-C10 alkyl, dialkylaminoalkylenyl, a nitrogen protecting group, or a linker to a solid support; R3 is OX1, SX1, or N(X1)2; each X1 is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(&boxH;NH)N(H)Z8, or C(&boxH;O)N(H)Z8; Z8 is H or C1-C8 alkyl; L1, L2 and L3 together form 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 the group consisting of oxygen, nitrogen, and sulfur, and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic; G 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(Q1)(Q2), O(Q1), halo, S(Q1), or CN; each q1 is, independently, from 2 to 10; each q2 is, independently, 0 or 1; m is 0, 1 or 2; pp is from 1 to 10; and q3is from 1 to 10 with the proviso that when pp is 0, q3 is greater than 1; Rt is a phosphorus protecting group of formula: each R10 is independently H or lower alkyl; W is an electron withdrawing group; p is 0 to 3; each Y2 is independently, O, CH2 or NH; each Z is independently O or S; each X is independently O or S; Q is a linker connected to a solid support, â€”OH or Oâ€”Pr where Pr is a hydroxyl protecting group; and n is 1 to about 100; and b) contacting said sample with a deprotecting reagent for a time and under conditions sufficient to remove said Rt groups from said oligomers to form a plurality of deprotected oligomers, wherein said deprotecting reagent comprises at least one aliphatic amine, the conjugate acid of said amine having a pKa of from about 8 to about 11, said deprotecting reagent optionally further comprising one or more solvents selected from the group consisting of aliphatic, haloaliphatic, cyanoaliphatic, aromatic and alkylaromatic solvents, provided said deprotecting reagent does not comprise a heterocyclic base solvent in addition to said aliphatic amine.