(2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol -Drug Synthesis Database

【结构式】

【分子编号】12229

【品名】(2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol

【CA登记号】

【分子式】C₁₃H₂₀O₄Se

【分子量】319.2594

【元素组成】C 48.91% H 6.31% O 20.05% Se 24.73%

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：(A)

Condensation of dimethyl aspartate (II) with benzyloxy carbonyl sarcosine (I) using DCI gave dimethyl benzyloxycarbonyl sarcosylaspartate (III). Removal of benzyloxycarbonyl function from (III) by catalytic hydrogenation or HBr-AcOH followed by cyclization, effected by storage over P2O5 in vacuo for 48 h, gave methyl (1-methyl-2,5-dioxopiperazin-3-yl)acetate (IV). When (IV) was reacted with ethylamine in a sealed tube for 36 h, it yielded N-ethyl-2-(1-methyl-2,5,dioxopiperazin-3-yl)acetamide (V). The compound (V) was reduced with LiAlH4 to give 1-methyl-3-(2-ethylamino)ethylpiperazine (VI). When (VI) was condensed with ethyl chloroformate (A) at pH 3-3.5, a mixture of monocarbamates (VIIa, VIIb) were obtained. Cyclization of the monocarbamates (VIIa, VIIb) were effected by treatment with sodium ethoxide to afford 3-ethyl-8-methyl-1,3,8-triazabicyclo[4.4.0]decan-2-one (centperazine). When (VI) was reacted with ethyl chloroformate (A) in the presence of NaOC2H5 or Et3N, the dicarbamate (VIII) was formed.

参考文献中间体

合成目标

【1】 Saxena, R.; et al.; Studies in potential filaricides. 5. 3-Ethyl-8-methyl-1,3,8-triazabicyclo[4.4.0]decan-2-one, a new antifilarial agent. J Med Chem 1971, 14, 10, 929.
【2】 Arya, V.P.; Centperazine. Drugs Fut 1980, 5, 5, 229.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(A)	12229	(2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol	C₁₃H₂₀O₄Se	详情	详情
(VIIa)	39052	ethyl ethyl[2-(4-methyl-2-piperazinyl)ethyl]carbamate	C₁₂H₂₅N₃O₂	详情	详情
(VIIb)	39053	ethyl 2-[2-(ethylamino)ethyl]-4-methyl-1-piperazinecarboxylate	C₁₂H₂₅N₃O₂	详情	详情
(I)	39046	(benzyloxy)carbonyl(methyl)carbamic acid	C₁₀H₁₁NO₄	详情	详情
(II)	39047	dimethyl 2-aminosuccinate	C₆H₁₁NO₄	详情	详情
(III)	39048	dimethyl 2-([2-[[(benzyloxy)carbonyl](methyl)amino]acetyl]amino)succinate	C₁₇H₂₂N₂O₇	详情	详情
(IV)	39049	methyl 2-(4-methyl-3,6-dioxo-2-piperazinyl)acetate	C₈H₁₂N₂O₄	详情	详情
(V)	39050	N-ethyl-2-(4-methyl-3,6-dioxo-2-piperazinyl)acetamide	C₉H₁₅N₃O₃	详情	详情
(VI)	39051	N-ethyl-2-(4-methyl-2-piperazinyl)-1-ethanamine; N-ethyl-N-[2-(4-methyl-2-piperazinyl)ethyl]amine	C₉H₂₁N₃	详情	详情
(VIII)	39054	ethyl 2-[2-[(ethoxycarbonyl)(ethyl)amino]ethyl]-4-methyl-1-piperazinecarboxylate	C₁₅H₂₉N₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXIV)

Finally, the first total synthesis of stavudine has also been described: Starting from epoxide (XXXIII), readily available in four steps from crotonaldehyde, compound (XXXIV) is obtained after reaction with selenophenol and diethylaluminum fluoride in dichloromethane. Reaction of (XXXIV) with hydrochloric acid in methanol-dichloromethane gives (XXXV), which is acetylated to give (XXXVI). Introduction of silylated thymine (XXIII) catalyzed by tert-butyldimethylsilyl triflate in dichloromethane affords compound (XXXVII), which is converted to (XXXVIII) on treatment with m-chloroperbenzoic acid in dichloromethane. Deprotection of (XXXVIII) provides an anomeric mixture of stavudine and its alpha-anomer (XXXIX).

参考文献中间体

合成目标

【1】 Gardiner, J.M.; Jung, M.E.; Synthesis of antiviral nucleosides from crotonaldehyde. Part 3. Total synthesis of didehydrodideoxythymidine (d4T). Tetrahedron Lett 1992, 33, 27, 3841-4.
【2】 Robinson, C.; Castaner, J.; Stavudine. Drugs Fut 1994, 19, 10, 925.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXIII)	12218	5-Methyl-2,4-bis[(trimethylsilyl)methyl]pyrimidine	C₁₃H₂₆N₂Si₂	详情	详情
(XXXIII)	12228	[3-(2,2-Dimethoxyethyl)-2-oxiranyl]methanol	C₇H₁₄O₄	详情	详情
(XXXIV)	12229	(2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol	C₁₃H₂₀O₄Se	详情	详情
(XXXV)	12230	[(2R,3S)-5-Methoxy-3-(phenylselanyl)tetrahydro-2-furanyl]methanol	C₁₂H₁₆O₃Se	详情	详情
(XXXVI)	12231	[(2R,3S)-5-methoxy-3-(phenylselanyl)tetrahydro-2-furanyl]methyl acetate	C₁₄H₁₈O₄Se	详情	详情
(XXXVII)	12185	2-Diazo-3-oxo-5-[4-oxo-3-(2-phenoxy-acetamido)-azetidin-2-yl]-pentanoic acid 4-nitro-benzyl ester	C₂₃H₂₁N₅O₈	详情	详情
(XXXVIII)	12233	[(2S)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl]methyl acetate	C₁₂H₁₄N₂O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(B)

This compound can be prepared in several ways: 1) By cyclization of 2-isopropylamino-4-methyl-4'-fluorobenzophenone (I) with potassium cyanate in hot acetic acid. 2) By cyclization of 2-isopropylamino-4-methyl-4'-fluorobenzophenone (I) with urea (A) or alkyl carbamates in the presence of an acid. 3) By condensation of 2-isopropylamino-4-methyl-4'-fluorobenzophenone (I) with ethyl chloroformate (B) at 100 C to give 2-(N ethoxycarbonyl-N-isopropylamino)-4-methyl-4'-fluorobenzophenone (II), followed by cyclization with ammonium acetate at 130 C.

参考文献中间体

合成目标

【1】 Serradell, M.N.; Blancafort, P.; Castañer, J.; Hilier, K.; Fluproquazone. Drugs Fut 1980, 5, 3, 130.
【2】 Hardtmann, G.E.; FR 2174828 .
【3】 Hardtmann, G.E.; DE 2230393 .
【4】 Gamboni, G.; DE 2753970 .
【5】 Hardtmann, G.E.; US 3937705 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	12229	(2R,3S)-5,5-Dimethoxy-3-(phenylselanyl)-1,2-pentanediol		C₁₃H₂₀O₄Se	详情	详情
(A)	19310	urea	57-13-6	CH₄N₂O	详情	详情
(I)	39078	(4-fluorophenyl)[2-(isopropylamino)-4-methylphenyl]methanone		C₁₇H₁₈FNO	详情	详情
(II)	39079	ethyl 2-(4-fluorobenzoyl)-5-methylphenyl(isopropyl)carbamate		C₂₀H₂₂FNO₃	详情	详情

Extended Information