isopropyl 2-(1-methyl-1H-indol-3-yl)ethanimidoate -Drug Synthesis Database

【结构式】

【分子编号】55755

【品名】isopropyl 2-(1-methyl-1H-indol-3-yl)ethanimidoate

【CA登记号】

【分子式】C₁₄H₁₈N₂O

【分子量】230.3098

【元素组成】C 73.01% H 7.88% N 12.16% O 6.95%

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：(VI)

Debenzylation of 1-benzyl-4-(1-indolyl)piperidine (I) with H2 and Pd(OH)2 leads to piperidine (II), which is further alkylated by 2-(bromomethyl)pyridine (III) to yield the pyridylmethyl piperidine (IV). Acylation of indole (IV) with oxalyl chloride produces the indoleglyoxylyl chloride (V). This is finally cyclized with the indolyl acetimidate (VI) in the presence of Et3N to produce the target bis-indolyl maleimide.

参考文献中间体

合成目标

【1】 Heath, W.F.H. Jr.; McDonald, J.H. III; Paal, M.; Ruther, G.; Schotten, T.; Stenzel, W. (Eli Lilly and Company); Protein kinase C inhibitors. EP 0817627; JP 1997507066; US 5545636; WO 9517182 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63739	1-(1-benzyl-4-piperidinyl)-1H-indole	C₂₀H₂₂N₂	详情	详情
(II)	63740	1-(4-piperidinyl)-1H-indole	C₁₃H₁₆N₂	详情	详情
(III)	27437	2-(bromomethyl)pyridine	C₆H₆BrN	详情	详情
(IV)	63741	1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indole	C₁₉H₂₁N₃	详情	详情
(V)	63742	2-oxo-2-{1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl}acetyl chloride	C₂₁H₂₀ClN₃O₂	详情	详情
(VI)	55755	isopropyl 2-(1-methyl-1H-indol-3-yl)ethanimidoate	C₁₄H₁₈N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

This compound has been obtained by two similar ways: The condensation of 6-iodo-1-methyl-1H-indole (I) with imidazole (II) by means of copper trifluoromethanesulfonate, 1,10-phenanthroline, Cs2CO3 and dibenzylideneacetone gives 6-(1-imidazolyl)-1-methyl-1H-indole (III), which is condensed with oxalyl chloride (IV) in dichloromethane to yield the adduct (V). Finally, this compound is cyclized with 2-(1-methyl-1H-indol-3-yl)acetimidic acid isopropyl ester (VI) by means of TEA in dichloromethane to afford the target pyrrolinedione. Alternatively, indole (I) and imidazole (II) are condensed by means of Pd2(dba)3, BINAP and tBu-ONa to give 6-(1-imidazolyl)-1-methyl-1H-indole (III), which is condensed with methoxalyl chloride (VII) in dichloromethane to yield the adduct (VIII). The reduction of (VIII) with NaH2PO2 affords the methyl acetate derivative (IX), which is treated with NH4OH to provide the acetamide derivative (X). Finally, this compound is cyclized with the methoxalyl derivative (XI) (obtained by condensation of 1-methyl-1H-indole (XII) with methoxalyl chloride (VII)) by means of tBu-ONa in THF to afford the target pyrrolinedione.

参考文献中间体

合成目标

【1】 Kong, N.; Lovey, A.; Specian, A.; et al.; Design and synthesis of novel orally bioavailable, water soluble bisindolylmaleimides as cell cycle inhibitors. Proc Am Assoc Cancer Res 2002, 43.
【2】 Lovey, A.J.; Fotouhi, N.; Kong, N. (F. Hoffmann-La Roche AG); Substd. pyrroles. WO 0146178 .

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)	55752	6-iodo-1-methyl-1H-indole		C₉H₈IN	详情	详情
(II)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(III)	55753	6-(1H-imidazol-1-yl)-1-methyl-1H-indole		C₁₂H₁₁N₃	详情	详情
(IV)	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(V)	55754	2-[6-(1H-imidazol-1-yl)-1-methyl-1H-indol-3-yl]-2-oxoacetyl chloride		C₁₄H₁₀ClN₃O₂	详情	详情
(VI)	55755	isopropyl 2-(1-methyl-1H-indol-3-yl)ethanimidoate		C₁₄H₁₈N₂O	详情	详情
(VII)	26971	2-methoxy-2-oxoacetyl chloride	5781-53-3	C₃H₃ClO₃	详情	详情
(VIII)	55756	methyl 2-[6-(1H-imidazol-1-yl)-1-methyl-1H-indol-3-yl]-2-oxoacetate		C₁₅H₁₃N₃O₃	详情	详情
(IX)	55757	methyl 2-[6-(1H-imidazol-1-yl)-1-methyl-1H-indol-3-yl]acetate		C₁₅H₁₅N₃O₂	详情	详情
(X)	55758	2-[6-(1H-imidazol-1-yl)-1-methyl-1H-indol-3-yl]acetamide		C₁₄H₁₄N₄O	详情	详情
(XI)	55759	methyl 2-(1-methyl-1H-indol-3-yl)-2-oxoacetate		C₁₂H₁₁NO₃	详情	详情
(XII)	14119	1-Methylindole; 1-Methyl-1H-indole	603-76-9	C₉H₉N	详情	详情

Extended Information