1-(1,3-benzodioxol-5-ylmethyl)-5-(chloromethyl)-1H-imidazole -Drug Synthesis Database

【结构式】

【分子编号】33672

【品名】1-(1,3-benzodioxol-5-ylmethyl)-5-(chloromethyl)-1H-imidazole

【CA登记号】

【分子式】C₁₂H₁₁ClN₂O₂

【分子量】250.68432

【元素组成】C 57.5% H 4.42% Cl 14.14% N 11.17% O 12.76%

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：(V)

The condensation of piperonylamine (I) with dihydroxyacetone dimer (II) in the presence of potassium thiocyanate produced the mercaptoimidazole (III), which was desulfurized upon treatment with nitric acid and sodium nitrite. The resulting (hydroxymethyl)imidazole (IV) was then converted to the corresponding chloride (V) employing thionyl chloride in chloroform.

参考文献中间体

合成目标

【1】 Lee, J.; Lee, H.; Shin, Y.; et al.; Synthesis and structure-activity relationships of 1-(1(3)H-imidazole-5(4)-yl)-methylpyrroles as farnesyl protein transferase inhibitors (FTPI). 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 210.
【2】 Lee, J.H.; Yoo, J.K.; Koh, J.S.; Choi, T.S.; Shin, Y.S.; Kim, K.H.; Jung, W.H.; Kim, J.H.; Lee, S.H.; Ahn, I.A.; Ro, S.G.; Lee, H.I.; Kim, H.S.; Chung, H.H.; Jeong, S.W.; Kwak, T.H. (LG Chem Ltd.); Imidazole derivs. having an inhibitory activity for farnesyl transferase and process for preparation thereof. WO 9928315 .

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)	33669	1,3-benzodioxol-5-ylmethylamine; 1,3-benzodioxol-5-ylmethanamine; 3,4-Methylendioxybenzylamine	2620-50-0	C₈H₉NO₂	详情	详情
(II)	20067	2,5-bis(hydroxymethyl)-1,4-dioxane-2,5-diol	89727-88-8	C₆H₁₂O₆	详情	详情
(III)	33670	[1-(1,3-benzodioxol-5-ylmethyl)-2-sulfanyl-1H-imidazol-5-yl]methanol		C₁₂H₁₂N₂O₃S	详情	详情
(IV)	33671	[1-(1,3-benzodioxol-5-ylmethyl)-1H-imidazol-5-yl]methanol		C₁₂H₁₂N₂O₃	详情	详情
(V)	33672	1-(1,3-benzodioxol-5-ylmethyl)-5-(chloromethyl)-1H-imidazole		C₁₂H₁₁ClN₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Horner-Emmons condensation of 1-naphthaldehyde (VI) with triethyl phosphonoacetate (VII) using DBU as the base afforded naphthylacrylate (VIII). This was reacted with tosylmethylisocyanide and potassium tert-butoxide to produce pyrrole (IX). Hydrolysis of the ester group of (IX) with KOH gave rise to the carboxylic acid (X), which was coupled with N-methylpiperazine (XI) employing EDC and HOBt or, alternatively, by previous conversion to the corresponding acid chloride with SOCl2. The resulting amide (XII) was finally alkylated at the pyrrole N atom with chloride (V) in the presence of NaH.

参考文献中间体

合成目标

【1】 Lee, J.; Lee, H.; Shin, Y.; et al.; Synthesis and structure-activity relationships of 1-(1(3)H-imidazole-5(4)-yl)-methylpyrroles as farnesyl protein transferase inhibitors (FTPI). 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 210.
【2】 Lee, J.H.; Yoo, J.K.; Koh, J.S.; Choi, T.S.; Shin, Y.S.; Kim, K.H.; Jung, W.H.; Kim, J.H.; Lee, S.H.; Ahn, I.A.; Ro, S.G.; Lee, H.I.; Kim, H.S.; Chung, H.H.; Jeong, S.W.; Kwak, T.H. (LG Chem Ltd.); Imidazole derivs. having an inhibitory activity for farnesyl transferase and process for preparation thereof. WO 9928315 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	33672	1-(1,3-benzodioxol-5-ylmethyl)-5-(chloromethyl)-1H-imidazole		C₁₂H₁₁ClN₂O₂	详情	详情
(VI)	12314	1-Naphthaldehyde	66-77-3	C₁₁H₈O	详情	详情
(VII)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(VIII)	25405	ethyl (E)-3-(1-naphthyl)-2-propenoate		C₁₅H₁₄O₂	详情	详情
(IX)	33673	ethyl 4-(1-naphthyl)-1H-pyrrole-3-carboxylate		C₁₇H₁₅NO₂	详情	详情
(X)	33674	4-(1-naphthyl)-1H-pyrrole-3-carboxylic acid		C₁₅H₁₁NO₂	详情	详情
(XI)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(XII)	33675	(4-methyl-1-piperazinyl)[4-(1-naphthyl)-1H-pyrrol-3-yl]methanone		C₂₀H₂₁N₃O	详情	详情

Extended Information