合成路线:The reaction of (I) with acetonitrile in sulfuric acid provides the amide (II),which after hydrolysis in 12N HCl/methanol yields the 4-amino derivative (III).Acylation of (III) with isobutyryl chloride followed by reduction with borane-methylsulfide complex gives the racemate (V),MK-927 (2).The resolution of MK-927 is accomplished through the di-p-toluoyl-D-tartaric acid salt.
参考文献标题:Thienothiopyran-2-sulfonamides: A novel class of water-soluble carbonic anhydrase inhibitors
文献作者:Ponticello,G.S.; Freedman,M.B.; Habecker,C.N.; Lyle,P.A.; Schwam,H.; Varga,S.L.; Christy,M.E.; Randall,W.C.; Baldwin,J.J.
参考来源:J Med Chem 1987,30591-7
合成路线:A new synthesis of MK-417 has been published:The reaction of thiophene (I) with butyllithium and sulfur in THF yields thiophene-2-thiol lithium salt (II) which,without isolation,is condensed with potassium 3-bromopropionate (III) in water - THF giving 3-(2-thienylthio)propanoic acid (IV).The cyclization of (IV) with trifluoroacetic anhydride in hot toluene affords 5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-one (V),which is oxidized with H2O2 and sodium tungstate in ethyl acetate - toluene to give the corresponding 7,7-dioxide (VI).The stereocontrolled reduction of (VI) with borane - methylsulfide and (S)-1-methyl-3,3-diphenyltetrahydropyrrolo[1,2-c][1,3,2]oxaazaborole as catalyst in THF yields (R)-(+)-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol 7,7-dioxide (VII),which is converted to the corresponding sodium salt (VIII) with sodium acetylide in THF.This salt (VIII),without isolation,is treated with p-toluenesulfonyl chloride to afford the corresponding tosylate (IX) which,also without isolation,is condensed with isobutylamine (X) to give (S)-(-)-4-(2-methylpropylamino)-5,6-dihydro-4H-thieno[2,3-b]thiopyran 7,7-dioxide (XI).The reaction of (XI),first with oleum and then with thionyl chloride,yields the corresponding 2-sulfonyl chloride (XII),which is finally treated with aqueous ammonium hydroxide.
参考文献标题:An asymmetric synthesis of MK-0417 - Observations on oxazaborolidine-catalyzed reductions
文献作者:Reamer,R.A.; Jones,T.J.; Jones,E.T.T.; Blacklock,T.J.; Grabowski,E.J.J.; Mathre,D.J.; Roberts,F.E.; Mohan,J.J.; Xavier,L.C.; Sohar,P.
参考来源:J Org Chem 1991,56(2),763
合成路线:The reaction of (I) with acetonitrile in sulfuric acid provides the amide (II),which after hydrolysis in 12N HCl/methanol yields the 4-amino derivative (III).Acylation of (III) with isobutyryl chloride followed by reduction with borane-methylsulfide complex gives the racemate (V),MK-927 (2).The resolution of MK-927 is accomplished through the di-p-toluoyl-D-tartaric acid salt.
参考文献标题:Anyiglaucoma thieno-thiopyran and thieno-thiepin sulfonamide derivatives,compositions,and method of use thereof.
文献作者:Baldwin,J.J.; Christy,M.E.; Ponticello,G.S.
参考来源:US 4677115
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