102-28-3Relevant articles and documents
Citric acid catalysed Beckmann rearrangement, under solvent free conditions
Thopate, Shankar Ramchandra,Kote, Santosh Rajaram,Rohokale, Sandeep Vasantrao,Thorat, Nitin Madhukar
, p. 124 - 125 (2011)
Citric acid is reported to be a highly efficient and eco-friendly catalyst for the Beckmann rearrangement under solvent free conditions.
Radical arylation of triphenyl phosphite catalyzed by salicylic acid: Mechanistic investigations and synthetic applications
Estruch-Blasco, Manel,Felipe-Blanco, Diego,Bosque, Irene,Gonzalez-Gomez, Jose C.
, p. 14473 - 14485 (2020)
A straightforward and scalable methodology to synthesize diphenyl arylphosphonates at 20 °C within 1-2 h is reported using inexpensive SA as the catalytic promoter of the reaction. Mechanistic investigations suggest that the reaction proceeds via radical-radical coupling, consistent with the so-called persistent radical effect. The reaction tolerated a wide range of functional groups and heteroaromatic moieties. The synthetic usefulness and the unique reactivity of the obtained phosphonates were demonstrated in different one-step transformations.
Preparation method of aminoacetanilide
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Paragraph 0046-0064, (2021/01/29)
The invention belongs to the technical field of dye intermediate production, and particularly relates to a preparation method of aminoacetanilide, which comprises the following steps of 1) adding an acetate compound, phenylenediamine and a catalyst triethylene diamine into a reactor, and uniformly mixing to obtain a mixed solution, 2) under the protection of nitrogen, heating the mixed solution to65-90 DEG C, dropwise adding acetic acid, and reacting for 4-9 hours after dropwise adding is finished, and 3) after the reaction is finished, cooling to 15-25 DEG C, standing for 5-8 hours, filtering, fully washing a filter cake with n-butyl alcohol, and drying in vacuum at 80 DEG C for 6 hours to obtain aminoacetanilide. Aminoacetanilide is synthesized by using an acetate method, acetic anhydride which is high in price and easy to prepare drugs is not used, the production cost is reduced, and the method is suitable for industrial production; the method has the advantages of few reaction steps, no generation of waste acid, waste water and waste salt and no pollution to the environment; the yield (based on the weight of phenylenediamine) of the aminoacetanilide product prepared by the method is up to 97% or above, and the purity is up to 98% or above.
2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase
Bayliss, Richard,Boxall, Kathy,Carbain, Benoit,Coxon, Christopher R.,Fry, Andrew M.,Golding, Bernard T.,Griffin, Roger J.,Hardcastle, Ian R.,Harnor, Suzannah J.,Mas-Droux, Corine,Matheson, Christopher J.,Newell, David R.,Richards, Mark W.,Sivaprakasam, Mangaleswaran,Turner, David,Cano, Céline
supporting information, p. 707 - 731 (2020/08/24)
Renewed interest in covalent inhibitors of enzymes implicated in disease states has afforded several agents targeted at protein kinases of relevance to cancers. We now report the design, synthesis and biological evaluation of 6-ethynylpurines that act as covalent inhibitors of Nek2 by capturing a cysteine residue (Cys22) close to the catalytic domain of this protein kinase. Examination of the crystal structure of the non-covalent inhibitor 3-((6-cyclohexylmethoxy-7H-purin-2-yl)amino)benzamide in complex with Nek2 indicated that replacing the alkoxy with an ethynyl group places the terminus of the alkyne close to Cys22 and in a position compatible with the stereoelectronic requirements of a Michael addition. A series of 6-ethynylpurines was prepared and a structure activity relationship (SAR) established for inhibition of Nek2. 6-Ethynyl-N-phenyl-7H-purin-2-amine [IC50 0.15 μM (Nek2)] and 4-((6-ethynyl-7H-purin-2-yl)amino)benzenesulfonamide (IC50 0.14 μM) were selected for determination of the mode of inhibition of Nek2, which was shown to be time-dependent, not reversed by addition of ATP and negated by site directed mutagenesis of Cys22 to alanine. Replacement of the ethynyl group by ethyl or cyano abrogated activity. Variation of substituents on the N-phenyl moiety for 6-ethynylpurines gave further SAR data for Nek2 inhibition. The data showed little correlation of activity with the nature of the substituent, indicating that after sufficient initial competitive binding to Nek2 subsequent covalent modification of Cys22 occurs in all cases. A typical activity profile was that for 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide [IC50 0.06 μM (Nek2); GI50 (SKBR3) 2.2 μM] which exhibited >5-10-fold selectivity for Nek2 over other kinases; it also showed > 50% growth inhibition at 10 μM concentration against selected breast and leukaemia cell lines. X-ray crystallographic analysis confirmed that binding of the compound to the Nek2 ATP-binding site resulted in covalent modification of Cys22. Further studies confirmed that 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide has the attributes of a drug-like compound with good aqueous solubility, no inhibition of hERG at 25 μM and a good stability profile in human liver microsomes. It is concluded that 6-ethynylpurines are promising agents for cancer treatment by virtue of their selective inhibition of Nek2. This journal is
