Process for the synthesis of oligomeric compounds

DETAILED DESCRIPTION What is claimed is: 1.
A compound having the formula: ##STR38## wherein: X.
sub.
4 is Z or H; Z is CN, a halogen radical, , alkaryl, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl; X.
sub.
1 is O or S; X.
sub.
2 is a halogen radical; and X.
sub.
3 is --N(R.
sub.
6).
sub.
2, or a heterocycloalkyl or heterocycloalkenyl ring containing from 4 to 7 atoms, and having up to 3 heteroatoms selected from nitrogen, sulfur, and oxygen.
2.
The compound of claim 1 wherein X.
sub.
4 is H; and Z is CN.
3.
The compound of claim 2 wherein --CH(X.
sub.
4)--Z is in the para position.
4.
The compound of claim 3 wherein X.
sub.
1 is O.
5.
The compound of claim 4 wherein X.
sub.
3 is --N(R.
sub.
6).
sub.
2 where R.
sub.
6 is isopropyl.
6.
The compound of claim 5 wherein X.
sub.
2 is chloro.




Description:
FIELD OF THE INVENTION This invention relates to methods for the preparation of oligomeric compounds having phosphite, phosphodiester, phosphorothioate, phosphorodithioate or other linkages, and to intermediates useful in their preparation.
BACKGROUND OF THE INVENTION Oligonucleotides and their analogs have been developed and used in molecular biology in a variety of procedures as probes, primers, linkers, adapters, and gene fragments.
Modifications to oligonucleotides used in these procedures include labeling with nonisotopic labels, e.
g.
fluorescein, biotin, digoxigenin, alkaline phosphatase, or other reporter molecules.
Other modifications have been made to the ribose phosphate backbone to increase the nuclease stability of the resulting analog.
Examples of such modifications include incorporation of methyl phosphonate, phosphorothioate, or phosphorodithioate linkages, and 2'-O-methyl ribose sugar units.
Further modifications include those made to modulate uptake and cellular distribution.
With the success of these compounds for both diagnostic and therapeutic uses, there exists an ongoing demand for improved oligonucleotides and their analogs