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Multistep Mechanochemical Synthesis of PZ-1190, a Multitarget Antipsychotic Agent
Canale, Vittorio ; Kaminski, Michal ; Trybala, Wojciech , et al. ACS Sustain. Chem. Eng.,2023,11(45):16156-16164. DOI: 10.1021/acssuschemeng.3c04023
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Abstract: A solid-state approach was used to synthesize compound PZ-1190, a multitarget ligand for serotonin and dopamine receptors with potential antipsychotic activity in rodents. Compared to the classical batch synthesis approach, the developed multistep mechanochem. protocol improved the overall yield (from 32% to 56%), reduced the reaction time (from 42 to 4 h), and decreased the use of toxic reagents and organic solvents. All synthesized intermediates and PZ-1190 were isolated in high purity by extraction without the requirement of chromatog. purification PZ-1190 was obtained in high enantiomeric purity (≥99% ee) with no impact of grinding processes on the integrity of stereocenter. The described procedures represent rare examples of mechanochem. reduction of a carboxylic function, which might open up the possibility to obtain crucial β- and γ-amino alcs. in a sustainable manner. The oxidation of an aliphatic alc. into an aldehyde using mechanochem. has also been reported for the first time. The obtained results confirmed the suitability of mechanochem. as a sustainable and efficient method of synthesizing candidates for preclin. development.
Keywords: Azinesulfonamide derivatives ; Multistep mechanochemicalsynthesis ; Medicinal mechanochemistry ; Green chemistry ; Antipsychotic agents
Purchased from AmBeed: 134441-93-3 ; 13139-15-6 ; 69610-40-8 ; 87691-87-0 ; 56502-01-3 ; 15761-39-4 ; 26250-84-0 ; 82010-31-9 ; 530-62-1 ; 846038-18-4 ; 198493-30-0 ; 88790-38-9 ; 13139-15-6 ; 347146-79-6 ...More
CAS No. : | 69610-40-8 | MDL No. : | MFCD00066232 |
Formula : | C10H19NO3 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | BFFLLBPMZCIGRM-QMMMGPOBSA-N |
M.W : | 201.26 | Pubchem ID : | 643448 |
Synonyms : |
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Chemical Name : | N-Boc-L-Prolinol |
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
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In chloroform; N,N-dimethyl-formamide; | (1) To a mixture of 530 mg of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 1.20 g of 1-t-butoxycarbonyl-L-prolinol and 8 ml of DMF was added 200 mg of 55percent sodium hydride while the former was stirred under ice cooling. The resultant mixture was stirred for further 15 minutes. The reaction mixture was poured into ice water and acidified with acetic acid. Crystals thus precipitated were collected by filtration. The thus-obtained crystals were dissolved in chloroform. The resultant solution was washed with water and then dried over anhydrous magnesium sulfate. Chloroform was distilled off. Crystals thus obtained were washed with diethyl ether and then dried, whereby 797 mg of (2'S)-7-[(1'-t-butoxycarbonyl-2'-pyrrolidinylmethyl)oxy]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid was obtained. |
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