1,3-二氢苯并[c]异噻唑2,2-二氧化物的合成工艺改进
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摘要
1,3-二氢苯并[c]异噻唑2,2-二氧化物是常见的药物骨架,本文以邻氯氯苄和亚硫酸钠为原料,经亲核取代、酰氯化、酰胺化及偶联环化反应,以55%的总收率和99%的纯度合成了1,3-二氢苯并[c]异噻唑2,2-二氧化物,其结构经~1H NMR,~(13)C NMR和FT-IR确证。
1,3-Dihydrobenzo[c]isothiazole 2,2-dioxide is prevalent moiety in many pharmaceuticals. It was synthesized using 1-chloro-2-(chloromethyl)benzene and sodium sulfite as raw materials through nucleophilic substitution, acyl chloride, amidation and coupling cyclization reaction in 55% total yield and up to 99% purity. The structure was confirmed by ~1H NMR, ~(13)C NMR and FT-IR.
1,3-Dihydrobenzo[c]isothiazole 2,2-dioxide is prevalent moiety in many pharmaceuticals. It was synthesized using 1-chloro-2-(chloromethyl)benzene and sodium sulfite as raw materials through nucleophilic substitution, acyl chloride, amidation and coupling cyclization reaction in 55% total yield and up to 99% purity. The structure was confirmed by ~1H NMR, ~(13)C NMR and FT-IR.
引文
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[2] BENOD C, SUBRA G, NAHOUM V, et al. N-1H-Benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists[J].Bioorg Med Chem,2008,16(7):3537-3549.
[3] XIN T, ZHANG C L, TAN C Y, et al. Biological evaluation and structure modification of (S)-3-aminopyrrolidine derivatives[J].Chem Res Chin Univ,2014,30(1):91-97.
[4] ZHAO H, THURKAUF D, HE S H, et al. Indoline and piperazine containing derivatives as a novel class of mixed D2/D4 receptor antagonists.part 1:Identification and structure-activity relationships[J].Bioorg Med Chem Lett,2002,12(21):3105-3109.
[5] WALKER D P, BI F C, KALGUTKAR A S, et al. Trifluoromethylpyrimidine-based inhibitors of proline-rich tyrosine kinase2(PYK2):Structure-activity relationships and strategies for the eliminationof reactive metabolite formation[J].Bioorg Med Chem Lett,2008,18(23):6071-6077.
[6] MALLINGER A,SCHIEMANN K,RINK C, et al. Discovery of potent,selective,and orally bioavailable smallmolecule modulators of the mediator complex-associated kinases CDK8 and CDK19[J].J Med Chem,2016,59(3):1078-1101.
[7] TSOUNG J, WANG Y, DJURIC S W. Expedient Diels-Alder cycloadditions with orthoquinodimethanes in a high temperature/pressure flow reactor[J].React Chem Eng,2017,2(4):458-461.
[8] PETIT E, BOSCH L, FONT J, et al. Tosvinyl and besvinyl as protecting groups of imides,azinones, nucleosides,sultams,and lactams. catalytic conjugate additions to tosylacetylene[J].J Org Chem,2014,79(18):8826-8834.
[9] WIDDOWSON K L, NIE H. IL-8 receptor antagonists:US 9832438[P].1998.
[10] BERSOT R, HUMPHRIES P. Carbazole-containing sulfonamides as cryptochrome modulators:US 2013170186 [P].2013.
[11] NAKAYAMA J, TANUMA M, HONDA Y, et al. Reaction of arylmethanesulfonyl and styrylmethanesulfonyl chlorides with triethylamine[J].Tetrahedron Lett,1984,25(40):4553-4556.
[12] CHIARINO D, CONTRI A M. 2,l-Benzisothiazoline 2,2-dioxide and derivatives[J].J Heterocyclic Chem,1986,23(6):1645-1645.
[13] ABRAMOVITCH R A, HARDER R R, HOLCOMB W D. Plash vacuum pyrolysis of α-toluenesulfonyl azide[J].HETEROCYCLES,1987,26(9):2327-2330.
[14] SASMAL P K, VAMSEEKRISHNA C, POTLURI V, et al. Substituted heterocyclic acetamides as kappa opioid receptor(KOR) agonists:US 2013131408[P].2013.
[15] SCHIEMANN K, STIEBER F, BLAGG J, et al. 2-Aminopyridine compounds:EP 2014063778[P].2014.