Method for palladium catalyzed carbon-carbon coulping and products

• US 5,428,149 A
• Filed: 06/14/1993
• Issued: 06/27/1995
• Est. Priority Date: 06/14/1993
• Status: Expired due to Term

• Current Assignee: Washington State University
• Original Assignee: Washington State University
• Inventors: Eaton, Bruce
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): WILSON, JAMES O
• Application Number:
  US08/076,735
• Time in Patent Office: 743 Days
• Field of Search: 536/28.1, 536/28.5, 536/28.53, 536/28.55, 536/28.52, 536/28.4, 536/28.54
• US Class Current: 536/28.55
• CPC Class Codes: B01J 2231/4255 Stille-type, i.e. RY + R'3SnR'', in which R is alkenyl, aryl, R' is alkyl and R'' is alkenyl or aryl
• CPC Class Codes: B01J 2531/824 Palladium
• CPC Class Codes: B01J 31/2404 Cyclic ligands, including e.g. non-condensed polycyclic ligands, the phosphine-P atom being a ring member or a substituent on the ring
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

This invention discloses an improved method for the preparation of a superior palladim catalyst that is capable of coupling vinyl and aryl stannanes to 2'"'"'-deoxy-5-iodouridine.

Claims

1. A method for the preparation of pyrimidine nucleosides modified at the 5-position of the pyrimidine ring from a pyrimidine starting material containing a halogen leaving group attached to the 5-position of the pyrimidine ring, such method comprising the steps of:

preparing a solution of a palladium catalyst of the formula PdL₃, wherein L is triphenyl phosphine (PPhd₃);

reacting said pyrimidine starting material with a tetraalkyl tin compound of the formula R'"'"'SnR₃ ", wherein R" is selected from the group consisting of an alkyl of C1-C4 carbon and R'"'"' is selected from the group consisting of a carbonyl of C1-C7 C1-C7 carbons, a carbalkoxy of C1-C5 carbons, an alkenyl of C1-C3 carbons, an alkoxy of C1-C4 carbons or phenyl (C₆ H₅), with the palladium catalyst; and

isolating and purifying said modified pyrimidine nucleoside.

2. The method of claim 1 wherein said pyrimidine starting material is a 5-halo-uridine.

3. The method of claim 2 wherein said 5-halo-uridine is 5-iodo-uridine.

4. The method of claim 1 wherein the catalyst is comprised of Pd(OAc)₂ and P(C₆ H₅)₃.

5. The method of claim 4 wherein the molar ratio of P(C₆ H₅)₃ to Pd(OAc)₂ is about 3.

6. The method of claim 1 wherein R'"'"' is:

##STR14## and wherein R₁, R₂ and R₃ are independently selected from the group consisting of;

H, CH₃, Si(CH₃)₃, OR, CHO, phenyl, wherein R is selected from the group consisting of an alkyl of C1-C2 carbons.

7. The method of claim 4 wherein said catalyst further comprises CuI.

8. The method of claim 4 wherein said catalyst solution is prepared in a solvent selected from the group consisting of THF, acetonitrile, oxane, acetone, tetrahydropyran and morpholine.

9. The method of claim 7 wherein the molar ration of P(C₆ H₅)₃, CuI and Pd(OAc)₂ is about 3:

3;

1.