Method for preparing radiolabeled thymidine having low chromophoric byproducts

• US 7,419,653 B2
• Filed: 11/22/2006
• Issued: 09/02/2008
• Est. Priority Date: 12/15/2003
• Status: Expired due to Term

• Current Assignee: Siemens Medical Solutions USA Incorporated (Siemens AG)
• Original Assignee: Siemens Medical Solutions USA Incorporated (Siemens AG)
• Inventors: Walsh, Joseph C., Padgett, Henry C., Ysaguirre, Tanea
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US11/603,703
• Publication Number:
  US 20070077198A1
• Time in Patent Office: 650 Days
• Field of Search: 424/1.11, 424/1.37, 424/1.65, 424/1.81, 424/1.85, 424/1.89, 424/9.1, 544/224, 544/242, 549/200
• US Class Current: 424/1.65
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: C07H 19/048 Pyridine radicals
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention is a method and related precursor for preparing ¹⁸F-FLT. The precursor has a butoxycarbonyl protecting group at the 5′-position that results in low amounts of chromophoric byproducts being formed during deprotection. The method for preparing ¹⁸F-FLT is efficient and makes the final purification step less complicated.

Claims

1. A compound having the following formula:

2. A compound having the following formula:

3. A compound according to claim 2, wherein P is selected from the group consisting of tert-butoxycarbamate, isopropyl carbamate, pivaloyloxymethyl carbamate, methyl carbamate, allyl carbamate, N-tetrahydropyran, N-tetrahydrofuran;

t-butylamide, and N-pyrrolidinomethylamide.

4. A compound according to claim 2, wherein P is t-butoxycarbonyl.

5. A compound according to claim 2, wherein L is a sulfonate ester.

6. A compound according to claim 2, wherein L is selected from the group consisting of benzenesulfonyl, methylsulfonyl, p-methylbenzenesulfonyl, 4-nitrobenzene sulfonyl, p-bromobenzenesulfonyl, trifluoromethylsulfonyl, trichloroacetimidate, 2,2,2-trifluoroethanesulfonyl, and imidazolesulfonyl.

7. A compound according to claim 2, wherein L is nosylate, tosylate, or mesylate.

8. A compound according to claim 2, wherein X is t-butoxycarbonyl, methyl, methoxymethyl ethyl, or isobutyl.

9. A compound having the following formula:

10. A compound according to claim 9, wherein P is selected from the group consisting of tert-butoxycarbamate, isopropyl carbamate, pivaloyloxymethyl carbamate, methyl carbamate, allyl carbamate, N-tetrahydropyran, N-tetrahydrofuran, t-butylamide, and N-pyrrolidinomethylamide.

11. A compound according to claim 9, wherein P is t-butoxycarbonyl.

12. A compound according to claim 9, wherein L is a sulfonate ester.

13. A compound according to claim 9, wherein L is selected from the group consisting of benzenesulfonyl, methylsulfonyl, p-methylbenzenesulfonyl, 4-nitrobenzene sulfonyl, p-bromobenzenesulfonyl, trifluoromethylsulfonyl, trichloroacetimidate, 2,2,2-trifluoroethanesulfonyl, and imidazolesulfonyl.

14. A compound according to claim 9, wherein L is nosylate, tosylate, or mesylate.