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【结 构 式】

【分子编号】51526

【品名】4-[([1-methyl-5-[1-(2-pyridinylcarbonyl)cyclopropyl]-1H-benzimidazol-2-yl]methyl)amino]benzonitrile

【CA登记号】

【 分 子 式 】C25H21N5O

【 分 子 量 】407.47484

【元素组成】C 73.69% H 5.19% N 17.19% O 3.93%

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:(XIII)

Lithiation of 2-bromopyridine (II) with BuLi, followed by addition to 1-phenylcyclopropanecarbonitrile (I), gave rise to ketone (III). Electrophilic nitration of the phenyl ring of (III) produced the nitro derivative (IV). The nitro group of (IV) was subsequently reduced by catalytic hydrogenation over Raney Ni to afford aniline (V), which was further acylated with trifluoroacetic anhydride, yielding amide (VI). A second nitration reaction in (VI) with HNO3-H2SO4 provided the nitro anilide (VII). Amide (VII) N-alkylation by means of iodomethane and K2CO3 gave the corresponding N-methyl derivative (VIII). The trifluoroacetamide function of (VIII) was then hydrolyzed under basic conditions to furnish the nitro aniline (IX), which was reduced to the phenylenediamine (X) by catalytic hydrogenation in the presence of Raney Ni. Acylation of (X) by N-(4-cyanophenyl)glycine (XI) yielded amide (XII). Benzimidazole (XIII) was then obtained by cyclization of (XII) in refluxing HOAc. The keto group of (XIII) was converted to the oxime derivative (XV) by condensation with ethyl (aminooxy)acetate (XIV). Finally, Pinner reaction of nitrile (XV) with ethanolic HCl, followed by treatment of the resulting imidate with ammonium carbonate provided the target amidine.

1 Kauffmann, I.; Ries, U.; Priepke, H.; Hauel, N.; Stassen, J.M.; Nar, H.; Wienen, W. (Boehringer Ingelheim Pharma KG); Benzimidazoles, production thereof and use thereof as medicaments. DE 19829964; EP 1095025; WO 0001704 .
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) 51516 1-Phenyl-1-cyclopropanecarbonitrile 935-44-4 C10H9N 详情 详情
(II) 29052 2-Bromopyridine;α-bromopyridine;α-bromoazine 109-04-6 C5H4BrN 详情 详情
(III) 51517 (1-phenylcyclopropyl)(2-pyridinyl)methanone C15H13NO 详情 详情
(IV) 51518 [1-(4-nitrophenyl)cyclopropyl](2-pyridinyl)methanone C15H12N2O3 详情 详情
(V) 51519 [1-(4-aminophenyl)cyclopropyl](2-pyridinyl)methanone C15H14N2O 详情 详情
(VI) 51520 2,2,2-trifluoro-N-[4-[1-(2-pyridinylcarbonyl)cyclopropyl]phenyl]acetamide C17H13F3N2O2 详情 详情
(VII) 51521 2,2,2-trifluoro-N-[2-nitro-4-[1-(2-pyridinylcarbonyl)cyclopropyl]phenyl]acetamide C17H12F3N3O4 详情 详情
(VIII) 51522 2,2,2-trifluoro-N-methyl-N-[2-nitro-4-[1-(2-pyridinylcarbonyl)cyclopropyl]phenyl]acetamide C18H14F3N3O4 详情 详情
(IX) 51523 [1-[4-(methylamino)-3-nitrophenyl]cyclopropyl](2-pyridinyl)methanone C16H15N3O3 详情 详情
(X) 51524 [1-[3-amino-4-(methylamino)phenyl]cyclopropyl](2-pyridinyl)methanone C16H17N3O 详情 详情
(XI) 51512 2-(4-cyanoanilino)acetic acid C9H8N2O2 详情 详情
(XII) 51525 2-(4-cyanoanilino)-N-[2-(methylamino)-5-[1-(2-pyridinylcarbonyl)cyclopropyl]phenyl]acetamide C25H23N5O2 详情 详情
(XIII) 51526 4-[([1-methyl-5-[1-(2-pyridinylcarbonyl)cyclopropyl]-1H-benzimidazol-2-yl]methyl)amino]benzonitrile C25H21N5O 详情 详情
(XIV) 51527 ethyl 2-(aminooxy)acetate C4H9NO3 详情 详情
(XV) 51528 ethyl 2-([[(E)-(1-[2-[(4-cyanoanilino)methyl]-1-methyl-1H-benzimidazol-5-yl]cyclopropyl)(2-pyridinyl)methylidene]amino]oxy)acetate C29H28N6O3 详情 详情
Extended Information