L-168049

4-[3-(5-溴-2-丙氧基苯基)-5-(4-氯苯基)-1H-吡咯-2-基]吡啶Chemical Name: 4-[3-(5-Bromo-2-propoxyphenyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl]pyridine
CAS No. 191034-25-0
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:Aldol condensation of 5-bromo-2-propoxybenzaldehyde (I) with 4'-chloroacetophenone in the presence of NaOH produced chalcone (III) (1),which was condensed with pyridine-4-carbaldehyde (IV) using NaCN as the catalyst to yield diketone (V).Finally,the target pyrrole was constructed by Paal-Knorr synthesis using diketone (V) and ammonium acetate in boiling AcOH.

合成路线:The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromobenzyl bromide (II) in the presence of n-butyllithium,followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III).Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V),which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI).Finally,Suzuki coupling of (VI) with 3-methoxybenzeneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.

合成路线:The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromo-2-fluorobenzyl bromide (II) in the presence of n-butyllithium,followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III).Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V),which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI).Finally,Suzuki coupling of (VI) with 5-butyl-2-thiopheneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.
📌 参考资料/链接:
参考文献标题:Substd.pyridyl pyrroles,compsns.containing such cpds.and methods of use
文献作者:De Laszlo,S.E.; Chang,L.L.; Kim,D.; Mantlo,N.B.(Merck & Co.,Inc.)
参考来源:EP 0859771; JP 1999514651; WO 9716442

📄 详细内容


合成路线:Aldol condensation of 5-bromo-2-propoxybenzaldehyde (I) with 4'-chloroacetophenone in the presence of NaOH produced chalcone (III) (1),which was condensed with pyridine-4-carbaldehyde (IV) using NaCN as the catalyst to yield diketone (V).Finally,the target pyrrole was constructed by Paal-Knorr synthesis using diketone (V) and ammonium acetate in boiling AcOH.

合成路线:The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromobenzyl bromide (II) in the presence of n-butyllithium,followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III).Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V),which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI).Finally,Suzuki coupling of (VI) with 3-methoxybenzeneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.

合成路线:The alkylation of 4-(dimethoxymethyl)pyridine (I) with 4-bromo-2-fluorobenzyl bromide (II) in the presence of n-butyllithium,followed by ketal hydrolysis with formic acid provided the diaryl ethanone (III).Further alkylation of (III) with 4-chlorophenacyl bromide (IV) employing sodium hexamethyldisilazide yielded diketone (V),which was cyclized in the presence of ammonium acetate in boiling AcOH to produce pyrrole (VI).Finally,Suzuki coupling of (VI) with 5-butyl-2-thiopheneboronic acid (VII) by means of Pd(PPh3)4 furnished the title compound.

参考文献标题:Substd.pyridyl pyrroles,compsns.containing such cpds.and methods of use
文献作者:de Laszlo,S.E.; Kim,D.; Chang,L.L.; Mantlo,N.B.(Merck & Co.,Inc.)
参考来源:US 5776954


合成路线:Aldol condensation of 5-bromo-2-propoxybenzaldehyde (I) with 4'-chloroacetophenone in the presence of NaOH produced chalcone (III) (1),which was condensed with pyridine-4-carbaldehyde (IV) using NaCN as the catalyst to yield diketone (V).Finally,the target pyrrole was constructed by Paal-Knorr synthesis using diketone (V) and ammonium acetate in boiling AcOH.

参考文献标题:The development of 2-pyridyl-3,5-diaryl-pyrroles a
文献作者:Li,B.; Kim,D.; MacCoss,M.; de Laszlo,S.E.; Koch,G.E.; hacker,C.; Mantlo,N.; Pivinichny,J.V.; Cascieri,M.A.; Hagmann,W.K.
参考来源:15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998,Edinburgh) 1998,Abst P.232


合成路线:Aldol condensation of 5-bromo-2-propoxybenzaldehyde (I) with 4'-chloroacetophenone in the presence of NaOH produced chalcone (III) (1),which was condensed with pyridine-4-carbaldehyde (IV) using NaCN as the catalyst to yield diketone (V).Finally,the target pyrrole was constructed by Paal-Knorr synthesis using diketone (V) and ammonium acetate in boiling AcOH.
参考文献标题:Potent,orally absorbed glucagon receptor antagonists
文献作者:De Laszlo,S.E.; Hacker,C.; Li,B.; Kim,D.; MacCoss,M.; mantlo,N.; Pivnichny,J.V.; Colwell,L.; Koch,G.E.; Cascieri,M.A.; Hagmann,W.K.
参考来源:Bioorg Med Chem Lett 1999,9(5),641


产品链接: CAS No. 191034-25-0››