合成路线:The cyclization of benzonitrile (I) with sodium azide by means of ZnCl2 in hot DMF gives 5-phenyltetrazole (II),which is condensed with trityl chloride (III) by means of TEA in THF to yield 5-phenyl-2-(triphenylmethyl)tetrazole (IV).The condensation of (IV) with 4-iodotoluene (V) by means of n-BuLi,ZnCl2,(PPh3)2NiCl2 and CH3MgCl in THF affords 5-(4'-methylbiphenyl-2-yl)-2-triphenylmethyltetrazole ?VI),which is finally brominated with N-bromosuccinimide (NBS) and AIBN in refluxing acetic acid to provide the target intermediate 5-[4'-(bromomethyl)biphenyl-2-yl]-2-(triphenylmethyl)tetrazole (VII).
参考文献标题:Ortho-lithiation process for the synthesis of 2-substd.1-(tetrazol-5-yl)benzenes
文献作者:Anderson,R.K.; King,A.O.; Shuman,R.F.(Merck & Co.,Inc.)
参考来源:US 5039814
合成路线:A synthesis of L-692429 has been reported:The cyclization of isobutene (I) with chlorosulfonyl isocyanate (II) gives 1-(chlorosulfonyl)-4,4-dimethylazetidin-2-one (III),which is condensed with 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (IV) by means of triethylamine in methanol to yield 3-methyl-3-(methylsulfonamido)-N-[2-oxo-2,3,4,5-tetrahydro-1H-1-benzaze pin-3(R)-yl]butyramide (V).The reaction of (V) with 2'-[1-(triphenylmethyl)tetrazol-5-yl]biphenyl-4-ylmethyl bromide (VI) by means of NaH in THF/DMF affords protected L-692429,which is finally deprotected by a treatment with 5N HCl.
参考文献标题:A novel 3-substituted benzazepinone growth hormone secretagogue (L-692,429)
文献作者:Schoen,W.R.; Pisano,J.M.; Prendergast,K.; Wyvratt,M.J.Jr.; Fisher,M.H.; Cheng,K.; Chan,W.W.; Butler,B.; Smith,R.G.; Ball,R.G.
参考来源:J Med Chem 1994,37(7),897
合成路线:A synthesis of L-692429 has been reported:The cyclization of isobutene (I) with chlorosulfonyl isocyanate (II) gives 1-(chlorosulfonyl)-4,4-dimethylazetidin-2-one (III),which is condensed with 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (IV) by means of triethylamine in methanol to yield 3-methyl-3-(methylsulfonamido)-N-[2-oxo-2,3,4,5-tetrahydro-1H-1-benzaze pin-3(R)-yl]butyramide (V).The reaction of (V) with 2'-[1-(triphenylmethyl)tetrazol-5-yl]biphenyl-4-ylmethyl bromide (VI) by means of NaH in THF/DMF affords protected L-692429,which is finally deprotected by a treatment with 5N HCl.
参考文献标题:A convergent synthesis of a novel non-peptidyl growth hormone secretagogue,L-692,429
文献作者:Bergan,J.J.; Reider,P.J.; McNamara,J.M.; Volante,R.P.; Bhupathy,M.
参考来源:Tetrahedron Lett 1995,36(52),9445
合成路线:The selective monoesterification of 2,2-dimethylsuccinic acid (VIII) with methanol and sulfuric acid gives 2,2-dimethylsuccinic acid 4-methyl ester (IX),which is submitted to degradation with diphenylphosphoryl azide,TEA and benzyl alcohol in refluxing benzene,yielding 3-(benzyloxycarbonylamino)-3-methylbutyric acid methyl ester (X).The hydrolysis of (X) with NaOH in methanol affords the corresponding butyric acid (XI).The hydrogenation of 3-azido-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (XII) with H2 over Pt/C in methanol gives the racemic 3-amino derivative (XIII),which is submitted to optical resolution by crystallization of the L-tartrate salt,yielding the 3(R)-amino derivative (XIV).The condensation of amine (XIV) with acid (XI) by means of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BTPF) and DIEA in dichloromethane affords the corresponding amide (XV),which is condensed with the tetrazole derivative (VII) by means of NaH in DMF to provide the protected adduct (XVI).Finally,this compound is deprotected by hydrogenation with H2 over Pd/C in methanol and a treatment with TFA.
参考文献标题:Synthesis and biological properties of (carboxyalkyl)amino-substituted bicyclic lactam inhibitors of angiotensin converting enzyme
文献作者:Watthey,J.W.; Stanton,J.L.; Desai,M.; Babiarz,J.E.; Finn,B.M.
参考来源:J Med Chem 1985,28(10),1511
产品链接: CAS No. 145455-23-8››