Process for preparing 5-amino-2,3-dihydrophthalazine-1,4-dione monosodium salt
Inventors
Henry, Mark O. • Lynn, William S.
Assignees
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Publication Number
US-9732043-B2
Publication Date
2017-08-15
Expiration Date
Abstract
The present invention comprises methods of manufacturing a highly purified, pharmaceutical grade phthalazinedione (for example, 5-amino-2,3-dihydrophthalazine-1,4-dione) for administration to a human or animal. The manufacturing methods identify and isolate starting materials (for example, 3-nitrophthalic acid), and prepare intermediate products (for example, 3-nitrophthalhydrazide), which are suitable for the commercial batch process production of highly purified and high-yielding intermediate products and final phthalazinedione products. In an embodiment, a solution of 3-nitrophthalhydrazide and sodium hydroxide in water is prepared and hydrogenated to yield 5-amino-2,3-dihydrophthalazine-1,4-dione.
Core Innovation
The invention describes a process for preparing 5-amino-2,3-dihydrophthalazine-1,4-dione monosodium salt (monosodium luminol) from 3-nitrophthalic acid. The process provides a mixture of 3-nitrophthalic acid and acetic acid and reacts the mixture with hydrazine hydrate to provide 3-nitrophthalhydrazide.
After forming the intermediate, the process provides a solution of 3-nitrophthalhydrazide and sodium hydroxide in water and hydrogenates the solution to provide 5-amino-2,3-dihydrophthalazine-1,4-dione monosodium salt. The disclosed manufacturing approach is directed to pharmaceutical-grade preparations, including high purity and GMP-reproducibility.
The partial content further indicates pharmaceutical-grade manufacturing of highly purified phthalazinediones under GMP, including the use of HPLC purity criteria for selecting and isolating high-purity starting material.
Claims Coverage
The document contains one independent claim directed to a process sequence for preparing 5-amino-2,3-dihydrophthalazine-1,4-dione monosodium salt, with dependent claims refining the process conditions and downstream provision of the product.
Hydrazide formation from 3-nitrophthalic acid in acetic acid with hydrazine hydrate
Providing a mixture of 3-nitrophthalic acid and acetic acid and reacting the mixture with hydrazine hydrate to provide 3-nitrophthalhydrazide.
Aqueous sodium hydroxide conversion with hydrogenation to monosodium salt
Providing a solution of 3-nitrophthalhydrazide and sodium hydroxide in water and hydrogenating the solution to provide 5-amino-2,3-dihydrophthalazine-1,4-dione monosodium salt.
The claim set further narrows the hydrogenation step by specifying temperature and pressure and a duration range, and narrows product provision by crystallizing the monosodium salt from ethanol.
Stated Advantages
High purity.
GMP-reproducibility.
Documented Applications
Pharmaceutical-grade preparations.
Pharmaceutical-grade manufacturing of highly purified phthalazinediones under GMP.
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