US Patent:
20060041114, Feb 23, 2006
Inventors:
Nanda Sinha - Boxboro MA, US
William Zedalis - Fitchburg MA, US
Gregory Miranda - Princeton MA, US
International Classification:
C07H 21/04
C07F 9/6512
C07D 275/06
US Classification:
536024300, 544243000, 544244000, 548210000
Abstract:
A process for the sysnthesis of oligonucleotides using phosphoramidite chemistry is provided. The process employs as activator a 1,1-dioxo-1,2-dihydro-1λ-benzo[d]isothiazol-3-one, preferably in the presence of an organic base. The 1,1-dioxo-1,2-dihydro-1λ-benzo[d]isothiazol-3-one is represented by the following structural formula: wherein p is 0 or an integer from 1 to 4; Xis O or S; R for each occurrence is a substituent, preferably each independently, a halo, a substituted or unsubstituted aliphatic group, —NRR, —OR, —OC(O)R, —C(O)OR, or cyano; or two adjacent R groups taken together with the carbon atoms to which they are attached form a six membered saturated or unsaturated ring; Rand Rare each, independently, —H, a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group; and Ris a substituted or unsubstituted aliphatic group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group. Preferred organic bases are pyridine, 3-methylpyridine, or N-methylimidazole.