Hydrazine → 1,4-Phthalazinedione
Reaction equation
[NH2:1]N.[C:3]1(=[O:24])[N:7](CCCCON=C(OCC)C)[C:6](=[O:19])[C:5]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:4]12>>[C:3]1(=[O:24])[C:4]2[C:5](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:6](=[O:19])[N:1]=[N:7]1Participants
Procedure
Briefly, N-(4-bromobutyl)phthalimide was treated with the anion of ethyl N-hydroxyacetimidate in tetrahydrofuran to yield ethyl N-[(4-phthalimidobutyl)oxy]acetimidate. The product was then treated with hydrazine to release the desired amine, ethyl N-[(4-aminobutyl)oxy]acetamidate, from the phthalimide. The desired amine was isolated from the crude product by removal of phthalazine-1,4-dione by filtration, and was coupled to biotin using dicyclohexyl carbodiimide and N-hydroxy succinimide in dimethylformamide. Acidic hydrolysis of the coupled product, ethyl N-[(4-biotinamidobutyl)oxy]acetamidate, gave the final product, N-(4-aminooxybutyl)biotinamide, V. Other analogous aminooxy linkers may be prepared by variations of the above synthetic procedure. The synthesis of biotin aminooxy linker V is described in more detail and summarized in the reaction scheme presented in Example 1.
Sources & evidence
- ORD record
- ord-5fa68ba57e3f496595e47bf7b61d2949
- Source dataset
- uspto-grants-1999_03
- Patent number
- US05880270
Reaction notes
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