Method for preparing radiolabeled thymidine having low chromophoric byproducts
View Patent ↗The invention is a method and related precursor for preparing 18 F-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 18 F-FLT is efficient and makes the final purification step less complicated.
1. A method for preparing a compound having the following formula:
comprising:
a. [ 18 F]fluorinating a compound having the following formula:
wherein P is an amine protecting group and L is a leaving group, to produce a compound having the formula:
wherein P is the same as defined above; and
b. removing the amine protecting group and Boc group to produce 18 F-FLT.
2. A method according to claim 1 , wherein P is selected from the group consisting of tert-butoxycarbamate, isopropyl carbamate, pivaloyloxymethyr, carbamate, methyl carbamate, allyl carbamate, N-tetrahydropyran, N-tetrahydrofuran; t-butylamide, and N-pyrrolidinomethylamlde.
3. A method according to claim 1 , wherein P is t-butoxycarbonyl.
4. A method according to claim 1 , wherein L is benzenesulfonyl, methylsulfonyt, p-methylbenzenesulfonyl, 4nitrobenzene sulfonyl, p-bromobenzenesulfonyl, trifluoromethylsulfonyl, trichloroacetimidate, 2,2,2-trifluoroethanesulfonyl, or imidazolesulfonyl.
5. A method according to claim 1 , wherein L is nosylate, tosylate, or mesylate.
6. A method according to claim 1 , wherein P is t-butoxycarbonyl and L is nosylate.
7. A method according to claim 1 , wherein the amine protecting group and Boc groups are removed by acid hydrolysis.
8. A method according to claim 1 , wherein the amine protecting group and Boc group are removed by treating the reaction product of step (a) with HCI, HBr, HOAc, H 2 SO 4 , HI, trimethylsilyllodide, or H 3 PO 4 .