ethyl 3-[2-(2-ethoxy-2-oxoethyl)-4,5-difluoro-1H-benzimidazol-1-yl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】31351

【品名】ethyl 3-[2-(2-ethoxy-2-oxoethyl)-4,5-difluoro-1H-benzimidazol-1-yl]propanoate

【CA登记号】

【分子式】C₁₆H₁₈F₂N₂O₄

【分子量】340.3268064

【元素组成】C 56.47% H 5.33% F 11.16% N 8.23% O 18.8%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(VII)

Addition of acrylonitrile (II) to 3,4-difluoro-2-nitroaniline (I) gave the anilinopropionitrile (III). Subsequent hydrogenation of the nitro group of (III) over Pd/C led to the phenylenediamine (IV), which was condensed with carbethoxyacetimidate-HCl (V) to produce the benzimidazole (VI). After conversion of the nitrile group of (VI) to ester (VII) with ethanolic HCl, Dieckmann condensation using NaOEt furnished the cyclic ketoester (VIII). Finally, reaction of (VIII) with 2,6-difluoroaniline (IX) in xylene yielded the target carboxamide.

参考文献中间体

合成目标

【1】 Maryanoff, B.E.; et al.; Potential anxiolytic agents. Pyrido[1, 2-a]benzimidazoles: A new structural class of ligands for the benzodiazepine binding site on GABA-A receptors. J Med Chem 1995, 38, 1, 16.
【2】 Nortey, S.O.; Sanfilippo, P.J.; Dubinsky, B.; Maryanoff, B.E.; McComsey, D.F.; Reitz, A.B.; Shank, R.P.; McNally, J.J.; Potential anxiolytic agents. 3. Novel A-ring modified pyrido[1,2-a]benzimidazoles. Bioorg Med Chem Lett 1999, 9, 11, 1547.

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)	31347	3,4-difluoro-2-nitrophenylamine; 3,4-difluoro-2-nitroaniline		C₆H₄F₂N₂O₂	详情	详情
(II)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(III)	31348	3-(3,4-difluoro-2-nitroanilino)propanenitrile		C₉H₇F₂N₃O₂	详情	详情
(IV)	31349	3-(2-amino-3,4-difluoroanilino)propanenitrile		C₉H₉F₂N₃	详情	详情
(V)	17929	ethyl 3-ethoxy-3-iminopropanoate	2318-25-4	C₇H₁₃NO₃	详情	详情
(VI)	31350	ethyl 2-[1-(2-cyanoethyl)-4,5-difluoro-1H-benzimidazol-2-yl]acetate		C₁₄H₁₃F₂N₃O₂	详情	详情
(VII)	31351	ethyl 3-[2-(2-ethoxy-2-oxoethyl)-4,5-difluoro-1H-benzimidazol-1-yl]propanoate		C₁₆H₁₈F₂N₂O₄	详情	详情
(VIII)	31352	ethyl 6,7-difluoro-3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxylate		C₁₄H₁₂F₂N₂O₃	详情	详情
(IX)	17933	2,6-Difluorophenylamine; 2,6-Difluoroaniline	5509-65-9	C₆H₅F₂N	详情	详情

Extended Information