Patent ID: 6465650
Filing Date: 2002-10-15
Classification: C07D,Y02P

Abstract:
A process for the preparation of a compound of the formula (I) or a salt thereof wherein PG is a trityl type protective group which is labile to weak acids, and is selected from triphenylmethyl (Trt), (4-methoxyphenyl)diphenylmethyl (Mmt), (4-methylphenyl)-diphenylmethyl (Mtt), di-(4-methoxyphenyl)phenylmethyl (Dmt), and 9-(9-phenyl)xanthenyl(pixyl); X is NH, O, or S; Y is CH2; and Bâ€² is a base selected from adenine, cytosine, guanine, thymine, uracil, purine, 2,6-di-aminopurine, 7-deazaadenine, 7-deazaguanine, N4N4-ethanocytosine, N6N6-ethano-2,6-diaminopurine, 5-methylcytosine, 5-(C2-C6)alkynyluracil, 5-(C2-C6)alkynylcytosine, 5-fluorouracil and pseudoisocytosine, wherein any exocyclic amino or hydroxyl group is protected by a protective group, or Bâ€² is further selected from imidazole, triazole, and nitroimidazole; which comprises reacting a compound of the formula (II) wherein PG and X are as defined above, and R1 is hydrogen or an ester protective group, with a compound of the formula (III) wherein Bâ€² and Y are as defined above, at 0-45Â° C. in a suitable solvent or mixtures of these solvents using a coupling reagent conventionally used in peptide chemistry, to give a compound of the formula (IV) â€ƒwherein PG, X, Bâ€², and R1 are as defined above, and subsequently converting this compound to a compound of the formula (I) by eliminating the ester protective group R1 under weakly alkaline conditions using alkali metal hydroxide solution, or by tertiary amine compounds in water, or enzymatically with the aid of esterases or lipases at 0-50Â° C. in a suitable solvent or mixtures of these solvents, and wherein the resulting compound of the formula I may, optionally, be converted to a salt.