2457-76-3Relevant articles and documents
NaI/PPh3-Mediated Photochemical Reduction and Amination of Nitroarenes
Qu, Zhonghua,Chen, Xing,Zhong, Shuai,Deng, Guo-Jun,Huang, Huawen
supporting information, p. 5349 - 5353 (2021/07/21)
A mild transition-metal- and photosensitizer-free photoredox system based on the combination of NaI and PPh3 was found to enable highly selective reduction of nitroarenes. This protocol tolerates a broad range of reducible functional groups such as halogen (Cl, Br, and even I), aldehyde, ketone, carboxyl, and cyano. Moreover, the photoredox catalysis with NaI and stoichiometric PPh3 provides also an alternative entry to Cadogan-type reductive amination when o-nitrobiarenes were used.
2-chloro-4-fluorobenzoic acid and preparation method thereof
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Paragraph 0039-0040, (2017/04/03)
The invention discloses 2-chloro-4-fluorobenzoic acid and a preparation method thereof. With m-chloroaniline as a raw material, the method comprises the following steps: realizing amino protection through 2-(trimethylsilyl) ethoxymethyl chloride; realizing formylation through a Vilsmeier-Haack reaction; oxidizing to obtain carboxylic acid; performing hydrogenation reduction of nitro; and performing a fluorination reaction to obtain 2-chloro-4-fluorobenzoic acid. The pesticide intermediate 2-chloro-4-fluorobenzoic acid disclosed by the invention is easy to prepare and suitable for batch production; and moreover, by adopting the cheap m-chloroaniline as a raw material and the substances with low volatility and low toxicity in the preparation process and by controlling the types and addition amount of the catalyst and oxidant, the product yield is more than or equal to 85%.
Benzoyl ring halogenated classical 2-amino-6-methyl-3,4-dihydro-4-oxo-5- substituted thiobenzoyl-7H-pyrrolo[2,3-d]pyrimidine antifolates as inhibitors of thymidylate synthase and as antitumor agents
Gangjee, Aleem,Jain, Hiteshkumar D.,McGuire, John J.,Kisliuk, Roy L.
, p. 6730 - 6739 (2007/10/03)
In an attempt to circumvent resistance to and toxicity of clinically used folate-based thymidylate synthase (TS) inhibitors that require folylpoly-γ-glutamate synthetase (FPGS) for their antitumor activity, we designed and synthesized two classical 6-5 ring-fused analogues, N-[4-[(2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio] -2′-fluorobenzoyl]-L-glutamic acid (4) and N-[4-[(2-amino-6-methyl-3,4- dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)thio]-2′-chlorobenzoyl] -L-glutamic acid (5), as TS inhibitors and antitumor agents. The key intermediates in the synthesis of these classical analogues were the mercaptans 10 and 11, which were obtained from the corresponding nitro compounds 6 and 7 respectively, by reduction of the nitro groups followed by diazotization of the amines. The syntheses of analogues 4 and 5 were achieved via the oxidative addition of the sodium salt of ethyl 2-halo-substituted-4-mercaptobenzoate (16 or 17) to 2-amino-6-methyl-3,4-dihydro-4-oxo-7H-pyirolo[2,3-d]pyrimidine (18) in the presence of iodine. The esters obtained from the reaction were deprotected and coupled with diethyl-L-glutamate followed by saponification. Compounds 4 and 5 were both more potent inhibitors of human TS (IC50 values of 54 and 51 nM, respectively) than were PDDF and the clinically used ZD1694 and LY231514. Compounds 4 and 5 were not substrates for human FPGS up to 250 μM. In addition, 4 and 5 were growth inhibitory against CCRF-CEM cells as well as a number of other tumor cell lines in culture, and protection studies established TS as the principal target of these analogues.
