5-(4-iodophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine -Drug Synthesis Database

【结构式】

【分子编号】39982

【品名】5-(4-iodophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine

【CA登记号】

【分子式】C₁₃H₁₃IN₂

【分子量】324.16417

【元素组成】C 48.17% H 4.04% I 39.15% N 8.64%

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：(XV)

The esterification of 3-(4-imidazolyl)-2(E)-propenoic acid (I) with SOCl2 and methanol gives the methyl ester (II), which is reduced with H2 over Pd/C yielding the propionic ester (III). The reduction of (III) with LiAlH4 affords 3-(4-imidazolyl)-1-propanol (IV), which is treated with N,N-dimethyl chloroformamide to afford 4-(3-hydroxypropyl)-N,N-dimethylimidazole-1-carboxamide (V). The mesylation of (V) with methanesulfonyl chloride to give the corresponding methanesulfonate (VI), which is condensed with alpha-bromo-4-iodotoluene (XII) by means of NH3 and treated with HCl yielding 3-[1-(4-iodobenzyl)imidazol-5-yl]-1-propanol (XIII). The reaction of (XIII) with SOCl2 affords the 3-chloropropyl derivative (XIV), which is cyclized by means of potassium tert-butoxide to give 5-(4-iodobenzyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine (XV). Finally, this compound is condensed with radiolabeled potassium cyanide by means of palladium tetrakis(triphenylphosphine).

参考文献中间体

合成目标

【1】 Allentoff, A.J.; et al.; Palladium-catalyzed aryl cynations in radiosynthesis: Synthesis of 14C-labeled fadrozole, a potent aromatase inhibitor. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 49.

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)	27420	Urocanic acid; (E)-3-(1H-imidazol-4-yl)-2-propenoic acid	104-98-3	C₆H₆N₂O₂	详情	详情
(II)	39976	methyl (E)-3-(1H-imidazol-4-yl)-2-propenoate		C₇H₈N₂O₂	详情	详情
(III)	39977	methyl 3-(1H-imidazol-4-yl)propanoate		C₇H₁₀N₂O₂	详情	详情
(IV)	21245	3-(1H-imidazol-4-yl)-1-propanol		C₆H₁₀N₂O	详情	详情
(V)	39978	4-(3-hydroxypropyl)-N,N-dimethyl-1H-imidazole-1-carboxamide		C₉H₁₅N₃O₂	详情	详情
(VI)	27902	N,N-dimethyl-4-[3-[(trimethylsilyl)oxy]propyl]-1H-imidazole-1-carboxamide		C₁₂H₂₃N₃O₂Si	详情	详情
(XII)	39980	1-(bromomethyl)-4-iodobenzene	16004-15-2	C₇H₆BrI	详情	详情
(XIII)	39979	3-[1-(4-iodobenzyl)-1H-imidazol-5-yl]-1-propanol		C₁₃H₁₅IN₂O	详情	详情
(XIV)	39981	5-(3-chloropropyl)-1-(4-iodobenzyl)-1H-imidazole		C₁₃H₁₄ClIN₂	详情	详情
(XV)	39982	5-(4-iodophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine		C₁₃H₁₃IN₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The protection of 3-(1H-imidazol-4-yl)-1-propanol (I) according to known techniques gives (II), which is condensed with 4-iodobenzyl bromide (III) by means of ammonia in acetonitrile, yielding 3-[1-(4-iodobenzyl)-1H-imidazol-5-yl)-1-propanol (IV). The reaction of (IV) with SOCl2 in dichloromethane affords the corresponding chloro derivative (V), which is cyclized by means of LDA and TMEDA in THF, affording 5-(4-iodophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine (VI). Finally, this compound is treated with (14C)-KCN and palladium tetrakis(triphenylphosphine) in refluxing THF.

参考文献中间体

合成目标

【1】 Markus, B.; Jones, L.; Duelfer, T.; Ray, T.; Wu, A.; Allentoff, A.J.; Ciszewska, G.; Palladium-catalyzed aryl cyanations with [C-14]KCN: Synthesis of C-14-labelled fadrozole, a potent aromatase inhibitor. J Label Compd Radiopharm 2000, 43, 11, 1075.

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)	21245	3-(1H-imidazol-4-yl)-1-propanol		C₆H₁₀N₂O	详情	详情
(II)	47910	N-(tert-butyl)-4-[3-[(trimethylsilyl)oxy]propyl]-1H-imidazole-1-carboxamide		C₁₄H₂₇N₃O₂Si	详情	详情
(III)	39980	1-(bromomethyl)-4-iodobenzene	16004-15-2	C₇H₆BrI	详情	详情
(IV)	39979	3-[1-(4-iodobenzyl)-1H-imidazol-5-yl]-1-propanol		C₁₃H₁₅IN₂O	详情	详情
(V)	39981	5-(3-chloropropyl)-1-(4-iodobenzyl)-1H-imidazole		C₁₃H₁₄ClIN₂	详情	详情
(VI)	39982	5-(4-iodophenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine		C₁₃H₁₃IN₂	详情	详情

Extended Information