Method for deuteration of a heterocyclic ring

• US 7,517,990 B2
• Filed: 11/07/2003
• Issued: 04/14/2009
• Est. Priority Date: 11/15/2002
• Status: Active Grant

• Current Assignee: FUJIFILM Wako Pure Chemical Corporation (Fujifilm Holdings Corporation)
• Original Assignee: WAKO Pure Chemical Industries Limited (Fujifilm Holdings Corporation)
• Inventors: Ito, Nobuhiro, Hirota, Kosaku, Maesawa, Tsuneaki, Muto, Kazushige, Sajiki, Hironao
• Primary Examiner(s): Wilson; James O
• Assistant Examiner(s): SACKEY, EBENEZER O
• Application Number:
  US10/534,344
• Publication Number:
  US 20060025596A1
• Time in Patent Office: 1,985 Days
• Field of Search: 546/184, 548/400
• US Class Current: 546/184
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 209/20 substituted additionally by nitrogen atoms, e.g. tryptophane
• CPC Class Codes: C07D 213/16 containing only one pyridine ring
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/54 having two double bonds between ring members or between ring members and non-ring members
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 235/06 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
• CPC Class Codes: C07D 239/54 as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 473/30 attached in position 6, e.g. hypoxanthine
• CPC Class Codes: C07H 19/067 with ribosyl as the saccharide radical
• CPC Class Codes: C07H 19/167 with ribosyl as the saccharide radical
• CPC Class Codes: Y02P 20/54 using solvents, e.g. supercritical solvents or ionic liquids

Abstract

The present invention relates to a method for deuteration of a heterocyclic ring, which comprises subjecting a compound having a heterocyclic ring to sealed refluxing state in a deuterated solvent in the presence of an activated catalyst selected form a palladium catalyst, a platinum catalyst, a rhodium catalyst, a ruthenium catalyst, a nickel catalyst and a cobalt catalyst. In accordance with a method of the present invention, a hydrogen atom belonging to a heterocyclic ring of a compound having a heterocyclic ring can be very efficiently deuterated because temperature of deuteration reaction can be maintained at higher than boiling point of the solvent.

Further, a method for deuteration of the present invention can be applied widely to deuteration of various compounds having a heterocyclic ring which are liable to decomposition under supercritical conditions or acidic conditions, leading to industrial and efficient deuteration of a compound having a heterocyclic ring.

Claims

1. A method for deuteration of a heterocyclic ring, which comprises subjecting a compound having a heterocyclic ring to a sealed refluxing state in a deuterated solvent in the presence of an activated palladium catalyst.

2. The method for deuteration according to claim 1, wherein the activated palladium catalyst is an activated palladium carbon.

3. The method for deuteration according to claim 1, wherein the activated palladium catalyst is one activated with hydrogen gas or heavy hydrogen gas present in a deuteration reaction system.

4. The method for deuteration according to claim 1, wherein the deuterated solvent is heavy water (D₂O).

5. The method for deuteration according to claim 1, wherein the heterocyclic ring of the compound having a heterocyclic ring is a 3 to 20 membered ring.