501-68-8Relevant academic research and scientific papers
Atom- and Mass-economical Continuous Flow Production of 3-Chloropropionyl Chloride and its Subsequent Amidation
Movsisyan, Marine,Heugebaert, Thomas S. A.,Roman, Bart I.,Dams, Rudolf,Van Campenhout, Rudy,Conradi, Matthias,Stevens, Christian V.
supporting information, p. 11779 - 11784 (2018/08/01)
3-Chloropropionyl chloride is a chemically versatile building block with applications in the field of adhesives, pharmaceuticals, herbicides and fungicides. Its current production entails problems concerning safety, prolonged reaction times and the use of excessive amounts of chlorinating reagents. We developed a continuous flow procedure for acid chloride formation from acrylic acid and a consecutive 1,4-addition of hydrogen chloride generating 3-chloropropionyl chloride, as presented in this paper. Up to 94 % conversion was reached in 25 minutes at mild temperatures and pressures. This continuous flow method offers a safer alternative and is highly efficient in terms of consumption of starting product and shorter residence time. Valorization of this building block is exemplified by the synthesis of beclamide, a compound with sedative and anticonvulsant properties. Over 80 % conversion towards this drug was achieved in 1 minute in a continuous flow setup. Further research is needed to telescope the synthesis of 3-chloropropionyl chloride and subsequent beclamide formation without intermediate purification.
Design, synthesis and biological evaluation of novel dicarbonylalkyl piperazine derivatives as neuroprotective agents
Wang, Wen-Ya,Shen, Cheng-Wu,Weng, Zhi-Jie,Wang, Tie-Chuang,Zhang, Chuang,Jin, Xun-Qi,Li, Jian-Qi
supporting information, p. 387 - 390 (2016/03/16)
In the search of novel neuroprotective agents with higher potency than our previously identified anti-ischemic stroke drug candidate 1, a series of novel dicarbonyl piperazine derivatives were synthesized and evaluated on their neuroprotective activity via oxygen-glucose deprivation test in the neuron-like PC12 cells, hypoxia tolerance model in mice and focal cerebral ischemia model in rats. The result obtained indicated that compounds 7f, 7k and 7o, exhibited neuroprotective activity. Particularly, compound 7o containing 2,5-dimethylpiperazin moiety, showed prolonged life time of mice and reduced cerebral infarction of rats, which provided a potential candidate for the development of neuroprotective agents.
In silico and experimental identification of non ulcerogenic antiinflammatory agents: 3-Thio substituted-4,5-diaryl-4H-1,2,4-triazoles
Khatale, Pravin N.,Sivakumar,Mahajan, Niranjan S.,Jawarkar, Rahul D.,Kedar, Chakor K.
, p. 890 - 899 (2014/08/05)
A new series of 4,5 diaryl-1,2,4-triazole-3-thione substituted carboxamides have been designed, synthesized and tested for their analgesic and antiinflammatory potential. All the tested compounds exhibit antiinflammatory activity comparable to that of standard drugs rofecoxib and diclofenac. Some compounds demonstrate significant analgesic activity in contrast to reference drugs. Compound 9c has emerged as a highly potent lead compound. Ulcerogenic studies of synthesized compounds and rofecoxib show nil or negligible ulcerogenic effect compared to diclofenac. In silico analysis (docking studies) of the most active compound 9c has revealed hypothetical binding mode of the target compound to the cyclooxygenase isoenzyme (COX-2). Docking study has anticipated stereoselective binding mode for the most active compound 9c.
Simple synthesis of amides and weinreb amides Using PPh3 or PolymerSupported PPh3 and Iodine
Kumar, Amit,Akula, Hari Kiran,Lakshman, Mahesh K.
experimental part, p. 2709 - 2715 (2010/08/05)
The combination of PPh3/I2 has been shown to be effective for the conversion of a range of carboxylic acids into secondary, tertiary, and Weinreb amides. Simplification of the procedure was possible with the use of polymer-supported PPh3/ I2. Weinreb amides produced with the use of polymer-supported PPh3 could be filtered through a short silica gel plug and used in further transformations. Thus, the use of polymer-supported PPh3 offers potential applicability to diversityoriented reactions. Formal total syntheses of apocynin and pratosine, as well as syntheses of anhydrolychorinone and hippadine, have been achieved through the use of this amide-forming method. An attempt has been made to gain insight into this reaction.
Synthesis and biological screening of novel derivatives of 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles
Manikrao, Anil M.,Fursule, Ravindra A.,Rajesh,Kunjwani, Harish K.,Sabale, Prafulla M.
experimental part, p. 1642 - 1647 (2011/03/17)
3-Mercapto-(4H)-1,2,4-triazole has been synthesized from 1-formylthiosemicarbazide. Different N-substituted β-chloropropionamides have been prepared by reacting substituted amines with β- chloropropionylchloride. Different Nsubstituted β-chloropropionamides have been condensed with 3-mercapto-(4H)-1,2,4-triazole in basic medium to obtain various 3-(N-substituted carboxamidoethylthio)-(4H)-1,2,4-triazoles. The structure of the synthesized compounds are confirmed by IR, 1H NMR spectra and elemental analysis. All the compounds have been screened for their analgesic, anti-inflammatory and anxiolytic activity.
Design, development, and scale-up of a selective meso-epoxide desymmetrization process
Varie, David L.,Beck, Christopher,Borders, Sandra K.,Brady, Molly D.,Cronin, Jason S.,Ditsworth, Tracy K.,Hay, David A.,Hoard, David W.,Hoying, Richard C.,Linder, Ryan J.,Miller, Richard D.,Moher, Eric D.,Remacle, Jacob R.,Rieck III, John A.,Anderson, David D.,Dodson, Paul N.,Forst, Mindy B.,Pierson, Duane A.,Turpin, Joseph A.
supporting information, p. 546 - 559 (2012/12/31)
A pilot-plant scale desymmetrization of the cyclic meso-epoxide 4b, using a chiral lithium amide prepared from symmetrical diamine 17, was designed and implemented to provide allylic alcohol 3b in high yield and greater than 99% ee. This chiral alcohol was converted to ketone 2b, a key intermediate in a new asymmetric synthesis of LY459477. Chiral diamine 17 was prepared from a readily available chiral precursor, (R)-α-methylbenzylamine, and could be recovered from the reaction mixture and reused. Studies performed to probe the mechanism of the rearrangement reaction of epoxide 4b showed that diamine 17 provided an optimal combination of selectivity and scaleability for this process.
Formation of acrylanilides, acrylamides, and amides directly from carboxylic acids using thionyl chloride in dimethylacetamide in the absence of bases
Cvetovich, Raymond J.,DiMichele, Lisa
, p. 944 - 946 (2012/12/23)
A general one-pot procedure is described that rapidly converts acrylic acid to anilides upon sequential treatment of the acid in dimethylacetamide (DMAC) with thionyl chloride and stoichiometric amounts of anilines in 88-98% yields, with DMAC offering rate and stability advantages over the use of DMF. The use of DMAC was extended to other organic acids in forming anilides. Benzylamine amides can also be formed using stoichiometric amounts of benzylamine and brought to completion by warming in the absence of additional base. In addition, it was shown that tert-butylamides can be easily formed with the addition of excess tert-butylamine at 20 °C.
Convenient Syntheses of Cyclic Carboxamides from α,β,γ,δ and ε-halocarboxamides under Phase Transfer Conditions
Okawara, Tadashi,Matsuda, Takashi,Furukawa, Mitsuru
, p. 1225 - 1233 (2007/10/02)
Piperazine-2,5-diones (2) were prepared by N-alkylation between two molecules of α-halocarboxamides (1) in the presence of a phase transfer catalyst in yields of 64-88percent. β,γ,δ and ε-Lactams (6,9 and 13) were similarly synthesized by intramolecular N-alkylation of the corresponding halocarboxamides (5, 8 and 12) under phase transfer conditions in 53-99percent yields.Keywords--piperazine-2,5-dione; β-lactam; γ, δ, and ε lactams; bis-β-lactam; phase transfer catalyst; intramolecular N-alkylation
