CAS: 160982-16-1; (S)-6-Chloro-4-Hydroxy-3,4-Dihydro-2H-Thieno[3,2-E][1,2]Thiazine 1,1-Dioxide

相似化合物

1413393-01-7 171274-01-4 174139-69-6

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3-(溴乙酰基)-5-氯-2-噻吩磺酰胺 3-(2-Bromoacetyl)-5-Chloro-Thiophene-2-Sulfonamide 160982-11-6
3-Acetyl-5-Chloro-N-[4-(2-Hydroxyethyl)Phenyl]-Thiophene-2-Sulfonamide 165117-08-8

3-(溴乙酰基)-5-氯-2-噻吩磺酰胺置于(+)-二异松蒎基氯硼烷,Sodium Hydroxide体系中,用 甲基叔丁基醚,水 用作溶剂,化学反应 5.5H,以77%的收率获得(S)-6-氯-3,4-二氢-2H-噻吩[3,2-E]-1,2-噻嗪-4-醇 1,1-二氧化氮
参考文献:Enantioselective Synthesis Of Brinzolamide (Al-4862),A New Topical Carbonic Anhydrase Inhibitor. The "dcat Route" To Thiophenesulfonamides
标题:Enantioselective Synthesis Of Brinzolamide (Al-4862),A New Topical Carbonic Anhydrase Inhibitor. The "dcat Route" To Thiophenesulfonamides
摘要:A Large Scale Synthesis Of The Topical Carbonic Anhydrase Inhibitors Al-4623A (13A . Hcl) And Al-4862 (13B) From 3-Acetyl-2,5-Dichlorothiophene ("Dcat",1) Is Described,Reaction Of 1 With Nasbn Gave Thioether 2,Which Was Converted Via Sulfenyl Chloride 3 And Sulfenamide 5 To Sulfonamide 6,Bromination Of 6 Gave Bromo Ketone 7,Which Upon Reduction With (+)-B-Chlorodiisopinocampheylborane And Cyclization Of The Resulting Bromohydrin Produced S Thieno[3,2-E]-1,2-Thiazine 8A (96% Ee) After Chromatography,Treatment Of 8A In Thf With N-Buli At-70 Degrees C Resulted In Li-Cl Exchange,Reaction Of The Thienyllithium With So2 And Hydroxylamine O-Sulfonic Acid Afforded Bis-Sulfonamide 11A,Protection Of 11A As The Acetinidate 12A,Followed By Tosylation And Amination,Gave R Amine 13A,The Synthesis Of 13B Proceeded Via Primary Sulfonamide 16,Which Was Brominated,Reduced,And Cyclized To Give S Thieno[3,2-E]-1,2-Thiazine 18 (>98% Ee). By Virtue Of The Ionizable Nh,18 Was Separable From Reduction Byproducts By Base Extraction. Alkylation Of 18 With 3-Bromopropyl Methyl Ether Afforded 8B,Which Was Converted As Above,Via 11B,To Al-4862 (13B),These Procedures Provided Multihundred Gram Lots Of 13A And 13B.
Doi:10.1021/op9802125