benzyl 4-[[[(1R,2S)-1-(2-fluoro-4-pyridinyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl](methyl)amino]carbonyl]-1-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】35166

【品名】benzyl 4-[[[(1R,2S)-1-(2-fluoro-4-pyridinyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl](methyl)amino]carbonyl]-1-piperidinecarboxylate

【CA登记号】

【分子式】C₂₉H₂₉F₄N₃O₄

【分子量】559.5606928

【元素组成】C 62.25% H 5.22% F 13.58% N 7.51% O 11.44%

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：(XVI)

Keto oxime (IV) was converted to the syn amino alcohol (XII) by palladium-catalyzed hydrogenation. Subsequent N-methylation of (XII) to give (XIV) was then achieved via formylation of the primary amine to formamide (XIII) in refluxing ethyl formate, followed by borane reduction. Acylation of the secondary amine (XIV) with N-(benzyloxycarbonyl)piperidine-4-carbonyl chloride (XV) provided amide (XVI). After Swern oxidation of the alcohol group of (XVI), the keto amide (XVII) was cyclized to the desired imidazole (VIII) in boiling ammonium formate.

参考文献中间体

合成目标

【1】 Claiborne, C.F.; et al.; An efficient synthesis of tetrasubstituted imidazoles from N-(2-oxo)-amides. Tetrahedron Lett 1998, 39, 49, 8939.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	16602	ethyl formate	109-94-4	C₃H₆O₂	详情	详情
(IV)	35155	1-(2-fluoro-4-pyridinyl)-2-[3-(trifluoromethyl)phenyl]-1,2-ethanedione 1-oxime		C₁₄H₈F₄N₂O₂	详情	详情
(VIII)	35159	benzyl 4-[5-(2-fluoro-4-pyridinyl)-1-methyl-4-[3-(trifluoromethyl)phenyl]-1H-imidazol-2-yl]-1-piperidinecarboxylate		C₂₉H₂₆F₄N₄O₂	详情	详情
(XII)	35162	(1S,2R)-2-amino-2-(2-fluoro-4-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-1-ethanol		C₁₄H₁₂F₄N₂O	详情	详情
(XIII)	35163	(1R,2S)-1-(2-fluoro-4-pyridinyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethylformamide		C₁₅H₁₂F₄N₂O₂	详情	详情
(XIV)	35164	(1S,2R)-2-(2-fluoro-4-pyridinyl)-2-(methylamino)-1-[3-(trifluoromethyl)phenyl]-1-ethanol		C₁₅H₁₄F₄N₂O	详情	详情
(XV)	35165	benzyl 4-(chlorocarbonyl)-1-piperidinecarboxylate		C₁₄H₁₆ClNO₃	详情	详情
(XVI)	35166	benzyl 4-[[[(1R,2S)-1-(2-fluoro-4-pyridinyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl](methyl)amino]carbonyl]-1-piperidinecarboxylate		C₂₉H₂₉F₄N₃O₄	详情	详情
(XVII)	35167	benzyl 4-[[[(1R)-1-(2-fluoro-4-pyridinyl)-2-oxo-2-[3-(trifluoromethyl)phenyl]ethyl](methyl)amino]carbonyl]-1-piperidinecarboxylate		C₂₉H₂₇F₄N₃O₄	详情	详情

Extended Information