trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate -Drug Synthesis Database

【结构式】

【分子编号】27311

【品名】trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate

【CA登记号】149-73-5

【分子式】C₄H₁₀O₃

【分子量】106.1216

【元素组成】C 45.27% H 9.5% O 45.23%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

The reaction of 7-fluoro-1-methyl-3,1-benzoxazine-2,4-dione (I) with trimethylsulfoxonium iodide and NaH in DMSO gives the corresponding ylide (II), which is cyclized with methyl orthoformate (III) in refluxing ethanol-acetic acid.

参考文献中间体

合成目标

【1】 Davies, R.V.; Fraser, J.; Nichol, K.J.; Parkinson, R.; Sim, M.F.; Yates, D.B. (The Boots Company plc); 4-Quinolinones having antihypertensive activity. DE 3011994; US 4302460 .
【2】 Castaner, J.; Prous, J.; Pivopril. Drugs Fut 1986, 11, 3, 177.

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)	10803	7-Fluoro-1-methyl-2H-3,1-benzoxazine-2,4(1H)-dione		C₉H₆FNO₃	详情	详情
(II)	27310	2-[dimethyl(oxo)-lambda(6)-sulfanylidene]-1-[4-fluoro-2-(methylamino)phenyl]-1-ethanone		C₁₁H₁₄FNO₂S	详情	详情
(III)	27311	trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate	149-73-5	C₄H₁₀O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The reaction of 14C-labeled cyanhydric acid (I) with HCl and ethanol gives the iminoester (II), which by reaction with more ethanol in chloroform yields the labeled orthoester (III). The cyclization of the triaminopyrimidinone (IV) with orthoester (III) by means of Ms-OH in chloroform affords the chloropurine derivative (V), which is finally hydrolyzed with NaOH to afford the target compound, the 14C-labeled carbovir.

参考文献中间体

合成目标

【1】 Gopinathan, M.B.; Kepler, J.A.; Synthesis of carbon-14 labelled cis-2-amino-1,9-dihydro-9-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-H6-purine-6-one; [8-14C]carbovir: A promising anti-AIDS drug. J Label Compd Radiopharm 1991, 29, 6, 645.

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)	55517	nitrilomethane		CHN	详情	详情
(I)	55518	nitrilomethane		CHN	详情	详情
(II)	13213	ethyl iminoformate		C₃H₇NO	详情	详情
(II)	55519	ethyl iminoformate		C₃H₇NO	详情	详情
(III)	27311	trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate	149-73-5	C₄H₁₀O₃	详情	详情
(III)	55520	trimethoxymethane; dimethoxymethyl methyl ether		C₄H₁₀O₃	详情	详情
(IV)	17660	[(1S,4R)-4-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]-2-cyclopenten-1-yl]methanol		C₁₀H₁₄ClN₅O	详情	详情
(V)	17650	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情
(V)	55521	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol		C₁₁H₁₂ClN₅O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXVI)

Bromination of 1-(3-tert-butyl-4-hydroxyphenyl)ethanone (III) with NBS in acetonitrile yields 1-(3-bromo-5-tert-butyl-4-hydroxyphenyl)ethanone (XXV), which by protection with trimethyl orthoformate (XXVI) in the presence of (±)-CSA in MeOH affords the dimethyl acetal (XXVII). O-Methylation of phenol (XXVII) with MeI by means of K2CO3 in DMF provides 1-bromo-3-tert-butyl-5-(1,1-dimethoxyethyl)-2-methoxybenzene (XXVIII), which by Buchwald–Hartwig condensation with morpholine (XXIX) in the presence of Pd(OAc)2, BINAP and t-BuONa in DME leads to the Narylmorpholine (XXX). Bromination of compound (XXX) with PhNMe3Br3 in THF/MeOH generates the α-bromoacetal (XXXI), which, without isolation, is finally hydrolyzed by quenching in aqueous Na2S2O3 to give bromo ketone (IX) .

参考文献中间体

合成目标

【1】 Shimomura, N., Sasho, M., Kayano, A., Yoshizawa, K., Tsujii, M., Kuroda,H., Furukawa, K. (Eisai R&D Management Co., Ltd.). Processes for producing cyclic benzamidine derivative. CA 2515715, EP 1602646, US 2006058370, US 7375236, WO 2004078721.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXX）	68422	4-(3-(tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxyphenyl)morpholine		C₁₉H₃₁NO₄	详情	详情
(III)	68400	1-(3-tert-butyl-4-hydroxyphenyl)ethanone		C₁₂H₁₆O₂	详情	详情
(IX)	68405	2-bromo-1-(3-(tert-butyl)-4-methoxy-5-morpholinophenyl)ethanone		C₁₇H₂₄BrNO₃	详情	详情
(XXV)	68419	1-(3-bromo-5-(tert-butyl)-4-hydroxyphenyl)ethanone		C₁₂H₁₅BrO₂	详情	详情
(XXVI)	27311	trimethoxymethane;Trimethyl orthoformate;Methyl orthoformate	149-73-5	C₄H₁₀O₃	详情	详情
(XXVII)	68420	2-bromo-6-(tert-butyl)-4-(1,1-dimethoxyethyl)phenol		C₁₄H₂₁BrO₃	详情	详情
(XXVIII)	68421	1-bromo-3-(tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxybenzene;1-bromo-3-tert-butyl-5-(1,1-dimethoxyethyl)-2-methoxybenzene		C₁₅H₂₃BrO₃	详情	详情
(XXIX)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(XXXI)	68423	4-(5-(2-bromo-1,1-dimethoxyethyl)-3-(tert-butyl)-2-methoxyphenyl)morpholine		C₁₉H₃₀BrNO₄	详情	详情

Extended Information