ethyl 5-(5-[4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-hydroxyphenyl)methyl]phenyl]-2H-1,2,3,4-tetraazol-2-yl)pentanoate -Drug Synthesis Database

【结构式】

【分子编号】48163

【品名】ethyl 5-(5-[4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-hydroxyphenyl)methyl]phenyl]-2H-1,2,3,4-tetraazol-2-yl)pentanoate

【CA登记号】

【分子式】C₃₀H₄₀N₆O₃

【分子量】532.68624

【元素组成】C 67.64% H 7.57% N 15.78% O 9.01%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XI)

The condensation between aldehyde (VII), piperazine (III) and benzotriazole furnished adduct (VIII). The Grignard reagent (X), prepared by silylation of 3-bromophenol (IX) followed by reaction with Mg, was then condensed with the benzotriazolyl adduct (VIII) to give the (diarylmethyl)piperazine (XI). Finally, basic hydrolysis of the ethyl ester of (XI) yielded the title compound.

参考文献中间体

合成目标

【1】 Maw, G.N. (Pfizer Inc.); Anti-inflammatory piperazinyl-benzyl-tetrazole derivs. and intermediates thereof. EP 0983251; JP 2000513024; WO 9852929 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	20690	(2R,5S)-1-allyl-2,5-dimethylpiperazine		C₉H₁₈N₂	详情	详情
(VII)	48160	ethyl 5-[5-(4-formylphenyl)-2H-1,2,3,4-tetraazol-2-yl]pentanoate		C₁₅H₁₈N₄O₃	详情	详情
(VIII)	48161	ethyl 5-(5-[4-[[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](1H-1,2,3-benzotriazol-1-yl)methyl]phenyl]-2H-1,2,3,4-tetraazol-2-yl)pentanoate		C₃₀H₃₉N₉O₂	详情	详情
(IX)	20704	3-bromophenol	591-20-8	C₆H₅BrO	详情	详情
(X)	48162	bromo[3-[(trimethylsilyl)oxy]phenyl]magnesium		C₉H₁₃BrMgOSi	详情	详情
(XI)	48163	ethyl 5-(5-[4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-hydroxyphenyl)methyl]phenyl]-2H-1,2,3,4-tetraazol-2-yl)pentanoate		C₃₀H₄₀N₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

A related procedure for the synthesis of the precursor ethyl ester (XI) was also reported. The condensation between 4-formylbenzonitrile (IV), piperazine (III) and benzotriazole furnished the benzotriazolyl adduct (XII). Subsequent reaction of (XII) with the Grignard reagent (XIII) yielded the (diarylmethyl)piperazine (XIV). The cyano group of (XIV) was then converted to the tetrazole (XV) by treatment with trimethylsilyl azide and dibutyltin oxide. Alkylation of tetrazole (XV) with ethyl 5-bromovalerate (VI) gave rise to a mixture of 1-triazolyl (XVII) and 2-triazolylpentanoate (XVI). After desilylation of this mixture with tetraethylammonium fluoride, the desired 2-triazolyl derivative (XI) was isolated by column chromatography.

参考文献中间体

合成目标

【1】 Maw, G.N. (Pfizer Inc.); Anti-inflammatory piperazinyl-benzyl-tetrazole derivs. and intermediates thereof. EP 0983251; JP 2000513024; WO 9852929 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	20690	(2R,5S)-1-allyl-2,5-dimethylpiperazine		C₉H₁₈N₂	详情	详情
(IV)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(VI)	37151	ethyl 5-bromopentanoate	14660-52-7	C₇H₁₃BrO₂	详情	详情
(XI)	48163	ethyl 5-(5-[4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-hydroxyphenyl)methyl]phenyl]-2H-1,2,3,4-tetraazol-2-yl)pentanoate		C₃₀H₄₀N₆O₃	详情	详情
(XII)	48164	4-[[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](1H-1,2,3-benzotriazol-1-yl)methyl]benzonitrile		C₂₃H₂₆N₆	详情	详情
(XIII)	20706	bromo(3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)magnesium		C₁₂H₁₉BrMgOSi	详情	详情
(XIV)	48165	4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)methyl]benzonitrile		C₂₉H₄₁N₃OSi	详情	详情
(XV)	48166	(2R,5S)-1-allyl-4-[(R)-(3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)[4-(1H-1,2,3,4-tetraazol-5-yl)phenyl]methyl]-2,5-dimethylpiperazine; 3-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl][4-(1H-1,2,3,4-tetraazol-5-yl)phenyl]methyl]phenyl tert-butyl(dimethyl)silyl ether		C₂₉H₄₂N₆OSi	详情	详情
(XVI)	48168	ethyl 5-(5-[4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)methyl]phenyl]-1H-1,2,3,4-tetraazol-1-yl)pentanoate		C₃₆H₅₄N₆O₃Si	详情	详情
(XVII)	48167	ethyl 5-(5-[4-[(R)-[(2S,5R)-4-allyl-2,5-dimethylpiperazinyl](3-[[tert-butyl(dimethyl)silyl]oxy]phenyl)methyl]phenyl]-2H-1,2,3,4-tetraazol-2-yl)pentanoate		C₃₆H₅₄N₆O₃Si	详情	详情

Extended Information