(2-Butyl-4-chloro-1H-imidazol-5-yl)methyl tert-butyl(dimethyl)silyl ether; 2-Butyl-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-chloro-1H-imidazole -Drug Synthesis Database

【结构式】

【分子编号】13937

【品名】(2-Butyl-4-chloro-1H-imidazol-5-yl)methyl tert-butyl(dimethyl)silyl ether; 2-Butyl-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-chloro-1H-imidazole

【CA登记号】

【分子式】C₁₄H₂₇ClN₂OSi

【分子量】302.91946

【元素组成】C 55.51% H 8.98% Cl 11.7% N 9.25% O 5.28% Si 9.27%

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：(V)

A synthesis of [14C]-losartan has been described: The bromination of 4'-methylbiphenyl-2-carbonitrile (I) with Br2 and silver trifluoroacetate in dichloromethane gives 3'-bromo-4'-methylbiphenyl-2-carbonitrile (II), which is treated first with trimethylstannyl azide in refluxing toluene, and then with trityl chloride and triethylamine in hot dichloromethane, yielding 5-(3'-bromo-4'-methylbiphenyl-2-yl)-2-(triphenylmethyl)tetrazole (III). The bromination of (III) with N-bromosuccinimide (NBS) in refluxing carbon tetrachloride affords the corresponding bromomethyl derivative (IV), which is then condensed with 2-butyl-5-(tert-butyldimethylsilyloxymethyl)-4-chloro-1H-imidazole (V) by means of NaH in DMF to give (VI). The deprotection of (VI) with HCl in methanol yields the bromolosartan derivative (VII), which is finally tritiated by debromination with tritiated sodium borohydride and palladium acetate in methanol-THF.

参考文献中间体

合成目标

【1】 Rivero, R.A.; Chen, R.; Chakravarty, P.K.; Rosegay, A.; Greenlee, W.J.; Simpson, R.; The synthesis of [3H]-losartan, [3H]-L-158,641 and [3H]-L-158,809. Bioorg Med Chem Lett 1993, 3, 4, 557.

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)	13929	2-Cyano-4'-methylbiphenyl; 4'-Methyl[1,1'-biphenyl]-2-carbonitrile	114772-53-1	C₁₄H₁₁N	详情	详情
(II)	13934	3'-Bromo-4'-methyl[1,1'-biphenyl]-2-carbonitrile		C₁₄H₁₀BrN	详情	详情
(III)	13935	5-(3'-Bromo-4'-methyl[1,1'-biphenyl]-2-yl)-1-trityl-1H-1,2,3,4-tetraazole		C₃₃H₂₅BrN₄	详情	详情
(IV)	13936	5-[3'-Bromo-4'-(bromomethyl)[1,1'-biphenyl]-2-yl]-1-trityl-1H-1,2,3,4-tetraazole		C₃₃H₂₄Br₂N₄	详情	详情
(V)	13937	(2-Butyl-4-chloro-1H-imidazol-5-yl)methyl tert-butyl(dimethyl)silyl ether; 2-Butyl-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-chloro-1H-imidazole		C₁₄H₂₇ClN₂OSi	详情	详情
(VI)	13938	(1-[[3-Bromo-2'-(1-trityl-1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-2-butyl-4-chloro-1H-imidazol-5-yl)methanol		C₄₁H₃₆BrClN₆O	详情	详情
(VII)	13939	(1-[[3-Bromo-2'-(1H-1,2,3,4-tetraazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-2-butyl-4-chloro-1H-imidazol-5-yl)methanol		C₂₂H₂₂BrClN₆O	详情	详情

Extended Information