5-phenyl-2-trityl-2H-1,2,3,4-tetraazole -Drug Synthesis Database

【结构式】

【分子编号】36354

【品名】5-phenyl-2-trityl-2H-1,2,3,4-tetraazole

【CA登记号】

【分子式】C₂₆H₂₀N₄

【分子量】388.47176

【元素组成】C 80.39% H 5.19% N 14.42%

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：(VIII)

The condensation of 2-butyl-4-chloroimidazole-5-carbaldehyde (I) with 4-bromobenzyl bromide (II) by means of K2CO3 in dimethylacetamide gives 1-(4-bromobenzyl)-2-butyl-4-chloroimidazole-5-carbaldehyde (III), which is reduced with NaBH4 in methanol yielding the corresponding carbinol (IV). The condensation of (IV) with the phenylboronic acid (VI) by means of Pd(OAc)2 and PPh3 affords the biphenyl derivative (VI), which is finally detritylated with H2SO4 in acetonitrile. The intermediate phenylboronic acid (V) has been obtained as follows: The protection of 5-phenyltetrazole (VII) with trityl chloride and TEA in THF gives 5-phenyl-2-(triphenylmethyl)tetrazole (VII), which is then treated with isopropyl borate and BuLi in THF.

参考文献中间体

合成目标

【1】 Larsen, R.D.; et al.; Efficient synthesis of losartan, a nonpeptide angiotensin II receptor antagonist. J Org Chem 1994, 59, 21, 6391.

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)	13925	2-Butyl-4-chloro-1H-imidazole-5-carbaldehyde	83857-96-9	C₈H₁₁ClN₂O	详情	详情
(II)	16109	1-bromo-4-(bromomethyl)benzene; 4-Bromobenzyl bromide	589-15-1	C₇H₆Br₂	详情	详情
(III)	36350	1-(4-bromobenzyl)-2-butyl-4-chloro-1H-imidazole-5-carbaldehyde		C₁₅H₁₆BrClN₂O	详情	详情
(IV)	36351	[1-(4-bromobenzyl)-2-butyl-4-chloro-1H-imidazol-5-yl]methanol		C₁₅H₁₈BrClN₂O	详情	详情
(V)	36352	2-(2-trityl-2H-1,2,3,4-tetraazol-5-yl)phenylboronic acid		C₂₆H₂₁BN₄O₂	详情	详情
(VI)	13932	(2-Butyl-4-chloro-1-[[2'-(2-trityl-2H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-imidazol-5-yl)methanol		C₄₁H₃₇ClN₆O	详情	详情
(VII)	36353	5-phenyl-2H-1,2,3,4-tetraazole	18039-42-4	C₇H₆N₄	详情	详情
(VIII)	36354	5-phenyl-2-trityl-2H-1,2,3,4-tetraazole		C₂₆H₂₀N₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The cyclization of benzonitrile (I) with sodium azide by means of ZnCl2 in hot DMF gives 5-phenyltetrazole (II), which is condensed with trityl chloride (III) by means of TEA in THF to yield 5-phenyl-2-(triphenylmethyl)tetrazole (IV). The condensation of (IV) with 4-iodotoluene (V) by means of n-BuLi, ZnCl2, (PPh3)2NiCl2 and CH3MgCl in THF affords 5-(4'-methylbiphenyl-2-yl)-2-triphenylmethyltetrazole ?VI), which is finally brominated with N-bromosuccinimide (NBS) and AIBN in refluxing acetic acid to provide the target intermediate 5-[4'-(bromomethyl)biphenyl-2-yl]-2-(triphenylmethyl)tetrazole (VII).

参考文献中间体

合成目标

【1】 Fisher, M.H.; Wyvratt, M.J.; Schoen, W.R.; DeVita, R.J. (Merck & Co., Inc.); Benzo-fused lactams promote release of growth hormone. EP 0513974; JP 1994172316; US 5206235; WO 9216524 .
【2】 Anderson, R.K.; King, A.O.; Shuman, R.F. (Merck & Co., Inc.); Ortho-lithiation process for the synthesis of 2-substd. 1-(tetrazol-5-yl)benzenes. US 5039814 .

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)	25904	benzonitrile	100-47-0	C₇H₅N	详情	详情
(II)	36353	5-phenyl-2H-1,2,3,4-tetraazole	18039-42-4	C₇H₆N₄	详情	详情
(III)	28630	Triphenylchloromethane; 1-[Chloro(diphenyl)methyl]benzene; Trityl chloride	76-83-5	C₁₉H₁₅Cl	详情	详情
(IV)	36354	5-phenyl-2-trityl-2H-1,2,3,4-tetraazole		C₂₆H₂₀N₄	详情	详情
(V)	46620	1-iodo-4-methylbenzene		C₇H₇I	详情	详情
(VI)	46621	5-(4'-methyl[1,1'-biphenyl]-2-yl)-2-trityl-2H-1,2,3,4-tetraazole		C₃₃H₂₆N₄	详情	详情
(VII)	15538	5-[4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-2-trityl-2H-1,2,3,4-tetraazole	124750-51-2	C₃₃H₂₅BrN₄	详情	详情

Extended Information