ethyl N-[1-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]-N-methylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】12046

【品名】ethyl N-[1-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]-N-methylcarbamate

【CA登记号】

【分子式】C₂₃H₂₇FN₄O₂

【分子量】410.4915432

【元素组成】C 67.3% H 6.63% F 4.63% N 13.65% O 7.8%

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：(IV)

Mizolastine can be obtained by two related ways: 1) The condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with N-(4-piperidyl)carbamic acid ethyl ester (II) by means of NaOCH3 at 14 C gives N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]carbamic acid ethyl ester (III), which is methylated with methyl iodide and NaH in DMF to yield the corresponding N-methyl derivative (IV). The decarboxylative hydrolysis of (IV) with 48% HBr in acetic acid affords N-[1-[1-(4-fluorobenzyl)benzimidazol-2-yl]piperidin-4-yl]-N-methylamine (V), which is finally condensed with 2-(methylsulfanyl)pyrimidin-4(3H)-one (VI) by heating at 170 C. 2) Compound (V) can also be obtained by direct condensation of 2-chloro-1-(4-fluorobenzyl)benzimidazole (I) with 4-(methylamino)piperidine (VII) by means of K2CO3 in refluxing isoamyl alcohol.

参考文献中间体

合成目标

【1】 Mealy, N.; Ngo, J.; Castaner, J.; Mizolastine. Drugs Fut 1996, 21, 8, 799.
【2】 Manoury, P.; Binet, J.; Defosse, G. (Sanofi-Synthelabo ); EP 217700, FR 2587029, JP 87061979, US 4820710. EP 0217700; FR 2587029; JP 1987061979; US 4820710 .

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)	12043	1-(4-Fluorobenzyl-2-chlorobenzimidazol; 2-Chloro-1-(4-fluorobenzyl)-1H-benzimidazole; 1-(4-Fluorobenzyl)-2-chlorobenzimidazole	84946-20-3	C₁₄H₁₀ClFN₂	详情	详情
(II)	12044	ethyl N-(4-piperidinyl)carbamate		C₈H₁₆N₂O₂	详情	详情
(III)	12045	ethyl N-[1-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]carbamate		C₂₂H₂₅FN₄O₂	详情	详情
(IV)	12046	ethyl N-[1-[1-(4-fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]-N-methylcarbamate		C₂₃H₂₇FN₄O₂	详情	详情
(V)	12047	1-[1-(4-Fluorobenzyl)-1H-benzimidazol-2-yl]-N-methyl-4-piperidinamine; N-[1-[1-(4-Fluorobenzyl)-1H-benzimidazol-2-yl]-4-piperidinyl]-N-methylamine		C₂₀H₂₃FN₄	详情	详情
(VI)	12048	2-(Methylsulfanyl)-4(3H)-pyrimidinone		C₅H₆N₂OS	详情	详情
(VII)	12049	N-Methyl-N-(4-piperidinyl)amine; N-Methyl-4-piperidinamine		C₆H₁₄N₂	详情	详情

Extended Information