tert-butyl(dimethyl)silyl 1H-indol-5-yl ether; 5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indole -Drug Synthesis Database

【结构式】

【分子编号】57694

【品名】tert-butyl(dimethyl)silyl 1H-indol-5-yl ether; 5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indole

【CA登记号】

【分子式】C₁₄H₂₁NOSi

【分子量】247.41238

【元素组成】C 67.97% H 8.56% N 5.66% O 6.47% Si 11.35%

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：(XIV)

Hydrolysis and cyclization of the dibromo acetate (XI) under basic conditions provides the furoquinoline (XII). Cleavage of the methyl ether group of (XII) using HBr in boiling HOAc gives bromide (XIII). Subsequent bromide displacement in (XIII) by sodium acetate yields acetate ester (XIV), which is finally hydrolyzed to the desired alcohol with methanolic KOH.

参考文献中间体

合成目标

【1】 Chilin, A.; et al.; Synthesis and biological evaluation of a new furo(2,3-h)quinolin-2(1H)-one. J Med Chem 2002, 45, 5, 1146.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	57691	8-(2,3-dibromopropyl)-4-(methoxymethyl)-1,6-dimethyl-2-oxo-1,2-dihydro-7-quinolinyl acetate		C₁₈H₂₁Br₂NO₄	详情	详情
(XII)	57692	4-(methoxymethyl)-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one		C₁₆H₁₇NO₃	详情	详情
(XIII)	57693	5-Hydroxyindole; 5-Indolol	1953-54-4	C₈H₇NO	详情	详情
(XIV)	57694	tert-butyl(dimethyl)silyl 1H-indol-5-yl ether; 5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indole		C₁₄H₂₁NOSi	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

5-Hydroxyindole (I) is sequentially protected at the OH and NH groups to afford the silyl ether (II), and then the N-Boc derivative (III). Metalation of the protected indole (III) by means of tert-butyllithium, followed by reaction with trimethyl borate, provides the boronic acid (IV). Treatment of 2-chloro-3-quinolineboronic acid (V) with N-iodosuccinimide gives rise to 2-chloro-3-iodoquinoline (VI). This is subjected to Suzuki coupling with the indoleboronic acid (IV) to furnish the quinolinyl indole (VII). Desilylation of (VII) using triethylamine trihydrofluoride gives the hydroxy indole (VIII), which is alkylated with the chloro amine (IX) to produce the indolyl ether (X). Finally, hydrolysis of the 2-chloroquinoline moiety of (X) and simultaneous N-Boc group cleavage with 50% HOAc leads to the title compound.

参考文献中间体

合成目标

【1】 Fraley, M.E.; Kim, Y.; Karki, S.B. (Merck & Co., Inc.); Orally active salts with tyrosine kinase activity. WO 0232861 .

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)	57693	5-Hydroxyindole; 5-Indolol	1953-54-4	C₈H₇NO	详情	详情
(II)	57694	tert-butyl(dimethyl)silyl 1H-indol-5-yl ether; 5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indole		C₁₄H₂₁NOSi	详情	详情
(III)	57695	tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indole-1-carboxylate		C₁₉H₂₉NO₃Si	详情	详情
(IV)	57696	1-(tert-butoxycarbonyl)-5-{[tert-butyl(dimethyl)silyl]oxy}-1H-indol-2-ylboronic acid		C₁₉H₃₀BNO₅Si	详情	详情
(V)	57697	2-chloro-3-quinolinylboronic acid		C₉H₇BClNO₂	详情	详情
(VI)	57698	2-chloro-3-iodoquinoline		C₉H₅ClIN	详情	详情
(VII)	57699	tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-2-(2-chloro-3-quinolinyl)-1H-indole-1-carboxylate		C₂₈H₃₃ClN₂O₃Si	详情	详情
(VIII)	57700	tert-butyl 2-(2-chloro-3-quinolinyl)-5-hydroxy-1H-indole-1-carboxylate		C₂₂H₁₉ClN₂O₃	详情	详情
(IX)	57701	N-(2-chloroethyl)-N-(2-methoxyethyl)-N-methylamine; 2-chloro-N-(2-methoxyethyl)-N-methyl-1-ethanamine		C₆H₁₄ClNO	详情	详情
(X)	57702	tert-butyl 2-(2-chloro-3-quinolinyl)-5-{2-[(2-methoxyethyl)(methyl)amino]ethoxy}-1H-indole-1-carboxylate		C₂₈H₃₂ClN₃O₄	详情	详情

Extended Information