2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl triethylsilyl ether; 5-(1H-1,2,4-triazol-1-ylmethyl)-3-[2-[(triethylsilyl)oxy]ethyl]-1H-indole -Drug Synthesis Database

【结构式】

【分子编号】16863

【品名】2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl triethylsilyl ether; 5-(1H-1,2,4-triazol-1-ylmethyl)-3-[2-[(triethylsilyl)oxy]ethyl]-1H-indole

【CA登记号】

【分子式】C₁₉H₂₈N₄OSi

【分子量】356.54318

【元素组成】C 64.01% H 7.92% N 15.71% O 4.49% Si 7.88%

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：(IV)

1) The iodination of 4-(1,2,4-triazol-1-ylmethyl)aniline (I) with ICl and CaCO3 in methanol/water gives the 2-iodoaniline (II), which is cyclized with 1-(triethylsilyl)-4-(triethylsilyloxy)-1-butyne (III) by means of paladium acetate and Na2CO3 in hot DMF yielding 5-(1,2,4-triazol-1-ylmethyl)-3-[2-(triethylsilyloxy)ethyl]-1H-indole (IV). The desilylation of (IV) with HCl in methanol affords the corresponding alcohol (V), which is condensed with dimethylamine by means of methanesulfonyl chloride and triethylamine to give MK-0462 free base (VI). Finally, this compound is treated with benzoic acid in isopropyl alcohol/isopropyl acetate solution.

参考文献中间体

合成目标

【1】 Castañer, J.; Mealy, N.; Rabassseda, X.; MK-0462. Drugs Fut 1995, 20, 7, 676.
【2】 Lieberman, D.R.; Reamer, R.A.; Reider, P.J.; Cottrell, I.F.; Chen, C.-Y.; Verhoeven, T.R.; Larsen, R.D.; Houghton, P.G.; Synthesis of the 5-HT1D receptor agonist MK-0462 via a Pd-catalyzed coupling reaction. Tetrahedron Lett 1994, 35, 38, 6981-4.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10202	Benzoic acid	65-85-0	C₇H₆O₂	详情	详情
(I)	16860	4-(1H-1,2,4-triazol-1-ylmethyl)aniline; 4-(1H-1,2,4-triazol-1-ylmethyl)phenylamine		C₉H₁₀N₄	详情	详情
(II)	16861	2-iodo-4-(1H-1,2,4-triazol-1-ylmethyl)phenylamine; 2-iodo-4-(1H-1,2,4-triazol-1-ylmethyl)aniline		C₉H₉IN₄	详情	详情
(III)	16862	triethylsilyl 4-(triethylsilyl)-3-butynyl ether; triethyl[[4-(triethylsilyl)-3-butynyl]oxy]silane	160194-28-5	C₁₆H₃₄OSi₂	详情	详情
(IV)	16863	2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl triethylsilyl ether; 5-(1H-1,2,4-triazol-1-ylmethyl)-3-[2-[(triethylsilyl)oxy]ethyl]-1H-indole		C₁₉H₂₈N₄OSi	详情	详情
(V)	16864	2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]-1-ethanol		C₁₃H₁₄N₄O	详情	详情
(VI)	16865	N,N-dimethyl-2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]-1-ethanamine; N,N-dimethyl-N-[2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl]amine		C₁₅H₁₉N₅	详情	详情

Extended Information