新产品编号:1932131
Chemical Name: 4-[4-[1-[4-(1,3-Benzodioxol-5-ylsulfonyl)phenyl]-1-(1,3-dioxolan-2-yl)methyl]piperidin-1-yl]-1-(propylsulfonyl)piperidine
项目整合开发状态: Preclinical
项目研究机构: Schering-Plough (Originator)
合成路线:N-protection of the NH group of (I) with Boc2O and NaOH in Et2O yields derivative (II),which is then condensed with compound (III) by means of NaH in DMF to provide (IV).N-deprotection of (IV) by treatment with TFA in CH2Cl2 followed by reductocondensation with N-Boc-4-piperidone (V) in CH2Cl2 in the presence of Na(OAc)3BH affords compound (VI),which is oxidized with NaBO3.4H2O to provide (VII).Boc removal of (VII) by treatment with TFA in CH2Cl2,followed by reaction of the resulting secondary amine with sulfonyl chloride (VIII) in CH2Cl2 in the presence of Et3N,affords propylsulfonamide derivative (IX).Finally,treatment of (IX) with ethyleneglycol (X) in toluene in the presence of HC(OEt)3 and p-TsOH furnishes the target compound.
📌 参考资料/链接：
参考文献标题:Benzylidene ketal derivatives as M2 muscarinic receptor antagonists
文献作者:Chackalamannil,S.; Chen,L.-Y.; Boyle,C.D.; et al.
参考来源:220th ACS Natl Meet (Aug 20 2000,Washington DC) 2000,Abst MEDI 114
📄 详细内容
合成路线:N-protection of the NH group of (I) with Boc2O and NaOH in Et2O yields derivative (II),which is then condensed with compound (III) by means of NaH in DMF to provide (IV).N-deprotection of (IV) by treatment with TFA in CH2Cl2 followed by reductocondensation with N-Boc-4-piperidone (V) in CH2Cl2 in the presence of Na(OAc)3BH affords compound (VI),which is oxidized with NaBO3.4H2O to provide (VII).Boc removal of (VII) by treatment with TFA in CH2Cl2,followed by reaction of the resulting secondary amine with sulfonyl chloride (VIII) in CH2Cl2 in the presence of Et3N,affords propylsulfonamide derivative (IX).Finally,treatment of (IX) with ethyleneglycol (X) in toluene in the presence of HC(OEt)3 and p-TsOH furnishes the target compound.
参考文献标题:Benzylidine ketal derivatives as M2 muscarinic receptor antagonists
文献作者:Boyle,C.D.; Chackalamannil,S.; Chen,L.-Y.; Dugar,S.; Pushpavanam,P.; Billard,W.; Binch,H.III.; Crosby,G.; Cohen-Williams,M.; Coffin,V.L.; Duffy,R.A.; Ruperto,V.; Lachowicz,J.E.
参考来源:Bioorg Med Chem Lett 2000,10(24),2727