ethyl (E)-3-(1-naphthyl)-2-propenoate -Drug Synthesis Database

【结构式】

【分子编号】25405

【品名】ethyl (E)-3-(1-naphthyl)-2-propenoate

【CA登记号】

【分子式】C₁₅H₁₄O₂

【分子量】226.27496

【元素组成】C 79.62% H 6.24% O 14.14%

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：(III)

Horner-Emmons reaction of 1-naphthaldehyde (I) with triethyl phosphonoacetate (II) gave naphthyl propenoate (III), which was hydrogenated over Pd/C to afford propanoate (IV), and further reduced to alcohol (V) with LiAlH4. The required naphthyl propylamine (VIII) was then obtained by the sequence of conversion of (V) to mesylate (VI), displacement by NaN3, and reduction of the resulting azide (VII) with LiAlH4. After coupling of (VIII) with N-Boc-L-asparagine N-hydroxysuccinimidyl ester (IX) to give (X), the N-Boc group was deprotected using trifluoroacetic acid in CH2Cl2 to afford amine (XI). Subsequent coupling of (XI) with N-Boc-1-amino-1-cyclohexanecarboxylic acid (XII) by means of DCC and HOBt gave (XIII).

参考文献中间体

合成目标

【1】 Yao, Z.-J.; King, C.R.; Cao, T.; Kelley, J.; Milne, G.W.; Voigt, J.H.; Burke, T.R. Jr.; Potent inhibition of Grb2 SH2 domain binding by non-phosphate-containing ligands. J Med Chem 1999, 42, 1, 25.

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)	12314	1-Naphthaldehyde	66-77-3	C₁₁H₈O	详情	详情
(III)	25405	ethyl (E)-3-(1-naphthyl)-2-propenoate		C₁₅H₁₄O₂	详情	详情
(IV)	25406	ethyl 3-(1-naphthyl)propanoate		C₁₅H₁₆O₂	详情	详情
(V)	25407	3-(1-naphthyl)-1-propanol		C₁₃H₁₄O	详情	详情
(VI)	25408	3-(1-naphthyl)propyl methanesulfonate		C₁₄H₁₆O₃S	详情	详情
(VII)	25409	3-(1-naphthyl)propyl azide; 1-(3-azidopropyl)naphthalene		C₁₃H₁₃N₃	详情	详情
(VIII)	25410	3-(1-naphthyl)-1-propanamine; 3-(1-naphthyl)propylamine		C₁₃H₁₅N	详情	详情
(IX)	25411	tert-butyl (1S)-3-amino-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]-3-oxopropylcarbamate		C₁₃H₁₉N₃O₇	详情	详情
(X)	25412	tert-butyl (1S)-3-amino-1-([[3-(1-naphthyl)propyl]amino]carbonyl)-3-oxopropylcarbamate		C₂₂H₂₉N₃O₄	详情	详情
(XI)	25413	(2S)-2-amino-N(1)-[3-(1-naphthyl)propyl]butanediamide		C₁₇H₂₁N₃O₂	详情	详情
(XII)	25414	1-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid		C₁₂H₂₁NO₄	详情	详情
(XIII)	25415	tert-butyl 1-([[(1S)-3-amino-1-([[3-(1-naphthyl)propyl]amino]carbonyl)-3-oxopropyl]amino]carbonyl)cyclohexylcarbamate		C₂₉H₄₀N₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

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