New Invention Profile
| Publication No: | IN202211013919 [India] | Application No: | 202211013919 |
| Title: | A process for preparation of phthalazinone derivatives and uses thereof | ||
| Publication Date: | 12-01-2024 | File Date: | 14-03-2022 |
| Inventor(s): | Deblina Roy; Indranil Chatterjee; Gautam Panda | ||
| IPC Classification: | C07D237/32, C07F7/18, C07D231/12, C07F9/53, C07C1/34 | ||
| Abstract: | The present invention relates to a process for cost effective and efficient synthesis of phthalazinone compounds such as Olaparib [Compound 13] and another PARP inhibitor AZD2461 [Compound 13c] which is currently used to treat advanced ovarian cancer in patients with specific mutations and prior history of chemotherapy. The drawbacks of previous synthesis are: a) use of genotoxic NH2NH2; b) preparation of phosphonate and further wittig Reaction furnishing insoluble phosphine oxide which is difficult to remove. c) Use of costly 2-fluoro-5- formylbenzonitrile (Rs 21,360 for 5gm from Sigma Aldrich) d) high cost of these reagents is a disadvantage for large-scale production. We have completed new synthesis of Olaparib, its key starting materials and intermediates starting from commercially available cheap piperazine and cyclopropane carbonyl chloride. Our synthesis consists of these merits: a) Piperazine and cyclopropane carbonyl chloride are cheap; b) phosphonate free synthesis and avoided less soluble impurities coming from wittig reaction; c) Moderate temperature being employed during reactions. d) Generation of conjugated enolate from 2-acetylbenzoic acid to produce desired prefinal product via SNAr reaction. e) Solvent DMF and ethanol are used. f) Only four step synthesis with appreciable yield from process chemistry standpoint. We have synthesized 15 g of HPLC pure Olaparib molecule. | ||
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Industrial Applications
Chemistry, Chemical Processes Polymers [Chemistry, Chemical Processes]
Synhtesis Procesess [Drugs and Pharmaceuticals]