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【结 构 式】 
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【药物名称】L-168049 【化学名称】4-[3-(5-Bromo-2-propoxyphenyl)-5-(4-chlorophenyl)-1H-pyrrol-2-yl]pyridine 【CA登记号】191034-25-0 【 分 子 式 】C24H20BrClN2O 【 分 子 量 】467.7968 |
【开发单位】Merck & Co. (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, PHARMACOLOGICAL TOOLS, Glucagon Antagonists |
合成路线1
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.
| 【1】 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.; The development of 2-pyridyl-3,5-diaryl-pyrroles a. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.232. |
| 【2】 Li, B.; Hacker, C.; De Laszlo, S.E.; et al.; Potent, orally absorbed glucagon receptor antagonists. Bioorg Med Chem Lett 1999, 9, 5, 641. |
| 【3】 de Laszlo, S.E.; Kim, D.; Chang, L.L.; Mantlo, N.B. (Merck & Co., Inc.); Substd. pyridyl pyrroles, compsns. containing such cpds. and methods of use. US 5776954 . |
| 【4】 De Laszlo, S.E.; Chang, L.L.; Kim, D.; Mantlo, N.B. (Merck & Co., Inc.); Substd. pyridyl pyrroles, compsns. containing such cpds. and methods of use. EP 0859771; JP 1999514651; WO 9716442 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 23277 | 5-bromo-2-propoxybenzaldehyde | C10H11BrO2 | 详情 | 详情 | |
| (II) | 12685 | 4-Chloroacetophenone; 1-(4-Chlorophenyl)-1-ethanone; p-Chloroacetophenone | 99-91-2 | C8H7ClO | 详情 | 详情 |
| (III) | 23279 | (E)-3-(5-bromo-2-propoxyphenyl)-1-(4-chlorophenyl)-2-propen-1-one | C18H16BrClO2 | 详情 | 详情 | |
| (IV) | 17203 | 4-Pyridinecarboxaldehyde; isonicotinaldehyde | 872-85-5 | C6H5NO | 详情 | 详情 |
| (V) | 23281 | 2-(5-bromo-2-propoxyphenyl)-4-(4-chlorophenyl)-1-(4-pyridinyl)-1,4-butanedione | C24H21BrClNO3 | 详情 | 详情 |
Extended Information