2-iodo-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】38258

【品名】2-iodo-1-ethanol

【CA登记号】624-76-0

【分子式】C₂H₅IO

【分子量】171.96557

【元素组成】C 13.97% H 2.93% I 73.8% O 9.3%

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：

Alkylation of 5-iodovanillin (I) with iodoethanol gave hydroxyethyl ether (II). This was condensed with vinyl ketone (III) in the presence of the thiazolium salt (IV) to produce the 1,4-diketone (V). Subsequent reduction of (V) with NaBH4 afforded 1,4-diol (VI), which was cyclized with trifluoroacetic acid in chloroform to furnish a mixture of cis and trans diaryltetrahydrofurans. The required trans isomer (VII) was isolated by column chromatography, and then treated with methanesulfonyl chloride and triethylamine to give mesylate (VIII). Further condensation of (VIII) with 4-chlorothiophenol (IX) provided sulfide (X). Finally, displacement of the iodine atom with CuCN in boiling DMF produced the title nitrile.

参考文献中间体

合成目标

【1】 Cai, X.; et al.; (+-)-trans-2-[3-Methoxy-4-(4-chlorophenylthioethoxy)-5-(N-methyl-N-hydroxyureidyl)methylphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (CMI-392), a potent dual 5-lipoxygenase inhibitor and platelet-activating factor receptor antagonist. J Med Chem 1998, 41, 11, 1970.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	38258	2-iodo-1-ethanol	624-76-0	C₂H₅IO	详情	详情
(I)	12758	4-Hydroxy-3-iodo-5-methoxybenzaldehyde; 5-Iodovanillin	5438-36-8	C₈H₇IO₃	详情	详情
(II)	27940	4-(2-hydroxyethoxy)-3-iodo-5-methoxybenzaldehyde		C₁₀H₁₁IO₄	详情	详情
(III)	27941	1-(3,4,5-trimethoxyphenyl)-2-propen-1-one		C₁₂H₁₄O₄	详情	详情
(IV)	27942	3-benzyl-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride	4568-71-2	C₁₃H₁₆ClNOS	详情	详情
(V)	27943	1-[4-(2-hydroxyethoxy)-3-iodo-5-methoxyphenyl]-4-(3,4,5-trimethoxyphenyl)-1,4-butanedione		C₂₂H₂₅IO₈	详情	详情
(VI)	27944	1-[4-(2-hydroxyethoxy)-3-iodo-5-methoxyphenyl]-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol		C₂₂H₂₉IO₈	详情	详情
(VII)	27945	2-[2-iodo-6-methoxy-4-[(2S,5S)-5-(3,4,5-trimethoxyphenyl)tetrahydro-2-furanyl]phenoxy]-1-ethanol		C₂₂H₂₇IO₇	详情	详情
(VIII)	27946	2-[2-iodo-6-methoxy-4-[(2S,5S)-5-(3,4,5-trimethoxyphenyl)tetrahydro-2-furanyl]phenoxy]ethyl methanesulfonate		C₂₃H₂₉IO₉S	详情	详情
(IX)	27947	4-chlorobenzenethiol	106-54-7	C₆H₅ClS	详情	详情
(X)	27948	(2S,5S)-2-(4-[2-[(4-chlorophenyl)sulfanyl]ethoxy]-3-iodo-5-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran		C₂₈H₃₀ClIO₆S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The esterification of 2,2-dimethyl-thiopropionic acid (I) with 2-iodoethanol (II) and DBU in toluene gives the corresponding thioester (III), which is condensed with diisopropylamidophosphoryl dichloride (IV) by means of TEA in THF to afford the phosphoramidite (V). Finally, this compound is condensed with AZT (VI) by means of 1H-tetrazole and MCPBA or 1H-tetrazole and tert-butyl peroxide, both cases in THF.

参考文献中间体

合成目标

【1】 Lefebvre, I.; et al.; Mononucleoside phosphotriester derivatives with S-acyl-2-thioethyl bioreversible phosphate-protecting groups: Intracellular delivery of 3'-azido-2',3'-dideoxythymidine 5'-monophosphate. J Med Chem 1995, 38, 20, 3941.
【2】 Lannuzel, M.; et al.; Synthesis of the tBuSATE pronucleotide of AZT by two different synthetic approaches. Nucleosides Nucleotides 1999, 18, 4-5, 1001.
【3】 Lefebvre, I.; et al.; Synthesis, descomposition pathways and "in vitro" evaluation of bioreversible phosphotriesters of AZT. Nucleosides Nucleotides 1995, 14, 3-5, 763.

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)	38257	2,2-dimethylpropanethioic S-acid		C₅H₁₀OS	详情	详情
(II)	38258	2-iodo-1-ethanol	624-76-0	C₂H₅IO	详情	详情
(III)	38259	S-(2-hydroxyethyl) 2,2-dimethylpropanethioate		C₇H₁₄O₂S	详情	详情
(IV)	38260			C₆H₁₄Cl₂NOP	详情	详情
(V)	38261	S-[4-(diisopropylamino)-10,10-dimethyl-4,9-dioxo-3,5-dioxa-8-thia-4lambda(5)-phosphaundec-1-yl] 2,2-dimethylpropanethioate		C₂₀H₄₀NO₅PS₂	详情	详情
(VI)	25317	1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione	101703-35-9	C₁₀H₁₃N₅O₄	详情	详情

Extended Information