- Method for synthesizing 2-chloro/hydroxypyrimidine-5-carboxylic acid
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The invention discloses a method for synthesizing 2-chloro/hydroxypyrimidine-5-carboxylic acid, and belongs to the field of synthesis of pharmaceutical intermediates. The invention comprises the following steps: reacting 2-chloro-5-bromopyrimidine with Boc2O under action of an active metallic reagent; then, adding an aqueous acid solution or an aqueous alkali solution to reflux at room temperature; and treating to obtain 2-chloropyrimidine-5-carboxylic acid and 2-hydroxypyrimidine-5-carboxylic acid, respectively. The method avoids a problem of low yield during scale-up by a method of feeding CO2, has good batch-to-batch operation reproducibility, and provides a new way for production scale-up.
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Paragraph 0011; 0024-0026
(2019/03/29)
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- Inhibitors of NF-kappaB and AP-1 gene expression: SAR studies on the pyrimidine portion of 2-chloro-4-trifluoromethylpyrimidine-5-[N-(3', 5'-bis(trifluoromethyl)phenyl)carboxamide].
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We investigated the structure-activity relationship studies of N-[3, 5-bis(trifluoromethyl)phenyl][2-chloro-4-(trifluoromethyl)pyrimidin-5 -yl]carboxamide (1), an inhibitor of transcription mediated by both NF-kappaB and AP-1 transcription factors, with the goal of improving its potential oral bioavailability. Compounds were examined for cell-based activity, were fit to Lipinski's rule of 5, and were examined for potential gastrointestinal permeability using the intestinal epithelial cell line, Caco-2. Selected groups were substituted at the 2-, 4-, and 5-positions of the pyrimidine ring using solution-phase combinatorial methodology. The introduction of a fluorine in the place of 2-chlorine of 1 resulted in a compound with comparable activity. However, other substitutions at the 2-position resulted in a loss of activity. The trifluoromethyl group at the 4-position could be replaced with a methyl, ethyl, chlorine, or phenyl without a substantial loss of activity. The carboxamide group at the 5-position is critical for activity. If it was moved to the 6-position, the activity was lost. The 2-methyl analogue of 1 (81) showed comparable in vitro activity and improved Caco-2 permeability compared to 1.
- Palanki,Erdman,Gayo-Fung,Shevlin,Sullivan,Goldman,Ransone,Bennett,Manning,Suto
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p. 3995 - 4004
(2007/10/03)
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- Organomanganese(II) Reagents in the Synthesis of 5-Pyrimidinyl Ketones
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Substituted alkyl 5-pyrimidinyl ketones were formed from acid chlorides of pyrimidine-5-carboxylic acids and alkylmanganese(II) iodides.The corresponding alcohols were also formed in the case of sterically less requiring organomanganese reagents and the a
- Arukwe, Joseph,Undheim, Kjell
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p. 764 - 767
(2007/10/02)
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