diethyl (phenylsulfonyl)methylphosphonate -Drug Synthesis Database

【结构式】

【分子编号】23624

【品名】diethyl (phenylsulfonyl)methylphosphonate

【CA登记号】

【分子式】C₁₁H₁₇O₅PS

【分子量】292.292742

【元素组成】C 45.2% H 5.86% O 27.37% P 10.6% S 10.97%

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：(VI)

N-Boc-Homophenylalanine (I) was coupled to N,O-dimethyl hydroxylamine using DCC, and the resulting N-methoxy amide (II) was reduced to aldehyde (III) with LiAlH4. Sulfonyl phosphonate (VI), (prepared from methyl phenyl sulfone (IV) and diethyl chlorophosphate (V)), was then condensed with aldehyde (III) in the presence of NaH to provide the vinylogous sulfone (VII). Subsequent acid deprotection of the Boc group of (VII) yielded amine (VIII). This was finally coupled with mixed anhydride (X), (obtained from morpholinocarbonyl-phenylalanine (IX) and isobutyl chloroformate in the presence of N-methylmorpholine), to furnish the target amide.

参考文献中间体

合成目标

【1】 Rasnick, D.; Klaus, J.L.; Palmer, J.T. (Khepri Pharmaceuticals Inc.); Irreversible cysteine protease inhibitors containi. WO 9523222 .

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)	23619	(2S)-2-[(tert-butoxycarbonyl)amino]-4-phenylbutyric acid	100564-78-1	C₁₅H₂₁NO₄	详情	详情
(II)	23620	tert-butyl (1S)-1-[[methoxy(methyl)amino]carbonyl]-3-phenylpropylcarbamate		C₁₇H₂₆N₂O₄	详情	详情
(III)	23621	tert-butyl (1S)-1-formyl-3-phenylpropylcarbamate		C₁₅H₂₁NO₃	详情	详情
(IV)	23622	methyl phenyl sulfone; methyl(dioxo)phenyl-lambda(6)-sulfane	3112-85-4	C₇H₈O₂S	详情	详情
(V)	23623	Chlorophosphoric acid ethyl ester；Phosphorochloridic acid diethyl ester；Diethyl chlorophosphate;diethyl phosphorochloridate	814-49-3	C₄H₁₀ClO₃P	详情	详情
(VI)	23624	diethyl (phenylsulfonyl)methylphosphonate		C₁₁H₁₇O₅PS	详情	详情
(VII)	23625	tert-butyl (1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylcarbamate		C₂₂H₂₇NO₄S	详情	详情
(VIII)	23626	(1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylamine; (E,3S)-5-phenyl-1-(phenylsulfonyl)-1-penten-3-amine		C₁₇H₁₉NO₂S	详情	详情
(IX)	23627	(2S)-2-[(4-morpholinylcarbonyl)amino]-3-phenylpropionic acid		C₁₄H₁₈N₂O₄	详情	详情
(X)	23628	N-(4-Morpholinylcarbonyl)-L-phenylalanine ethoxycarbonyl anhydride		C₁₇H₂₂N₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Phosphonylation of the lithium anion of phenyl methyl sulfone (I) with diethyl chlorophosphate afforded the sulfonyl phosphonate (II). This was condensed with N-Boc-L-homophenylalaninal (III) under Wadsworth-Emmons conditions to furnish the vinyl sulfone (IV). After acidic Boc group cleavage, the resultant amine (V) was coupled with the N-carbamoyl phenylalanine (VI), via the corresponding mixed anhydride with isobutyl chloroformate, to afford the target amide.

参考文献中间体

合成目标

【1】 Palmer, J.T.; Rasnick, D.; Klaus, J.L. (Celera Genomics); Irreversible cysteine protease inhibitors containing vinyl groups conjugated to electron withdrawing groups. US 6287840 .

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)	23622	methyl phenyl sulfone; methyl(dioxo)phenyl-lambda(6)-sulfane	3112-85-4	C₇H₈O₂S	详情	详情
(II)	23624	diethyl (phenylsulfonyl)methylphosphonate		C₁₁H₁₇O₅PS	详情	详情
(III)	23621	tert-butyl (1S)-1-formyl-3-phenylpropylcarbamate		C₁₅H₂₁NO₃	详情	详情
(IV)	23625	tert-butyl (1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylcarbamate		C₂₂H₂₇NO₄S	详情	详情
(V)	23626	(1S,2E)-1-phenethyl-3-(phenylsulfonyl)-2-propenylamine; (E,3S)-5-phenyl-1-(phenylsulfonyl)-1-penten-3-amine		C₁₇H₁₉NO₂S	详情	详情
(VI)	56040	(2S)-2-{[(4-methyl-1-piperazinyl)carbonyl]amino}-3-phenylpropanoic acid		C₁₅H₂₁N₃O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The Horner-Wadsworth-Emmons olefination of N-(tert-butoxycarbonyl)-L-homophenylalaninal (I) with phosphonate (II) by means of NaH in THF gives the vinylsulfonate (III), which is treated with tetrabutylammonium iodide and triphosgene to yield the sulfonyl chloride (IV). The reaction of (IV) with O-benzylhydroxylamine in dichloromethane affords the N-sulfonylhydroxylamine derivative (V), which is deprotected with TFA in dichloromethane, providing compound (VI) with a free amino group. Finally, this compound is condensed with N-(morpholin-4-ylcarbonyl)-L-phenylalanine (VII) by means of HOBt, EDC and NMM in DMF, giving rise to the target amide.

参考文献中间体

合成目标

【1】 Roush, W.R.; et al.; Potent second generation vinyl sulfonamide inhibitors of the trypanosomal cysteine protease cruzain. Bioorg Med Chem Lett 2001, 11, 20, 2759.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	23624	diethyl (phenylsulfonyl)methylphosphonate	C₁₁H₁₇O₅PS	详情	详情
(II)	51650	ethyl dimethoxy(oxo)phosphoranesulfonate	C₄H₁₁O₆PS	详情	详情
(III)	51651	ethyl (E,3S)-3-[(tert-butoxycarbonyl)amino]-5-phenyl-1-pentene-1-sulfonate	C₁₈H₂₇NO₅S	详情	详情
(IV)	51652	tert-butyl (1S,2E)-3-(chlorosulfonyl)-1-phenethyl-2-propenylcarbamate	C₁₆H₂₂ClNO₄S	详情	详情
(V)	51653	tert-butyl (1S,2E)-3-[[(benzyloxy)amino]sulfonyl]-1-phenethyl-2-propenylcarbamate	C₂₃H₃₀N₂O₅S	详情	详情
(VI)	51654	(E,3S)-3-amino-N-(benzyloxy)-5-phenyl-1-pentene-1-sulfonamide	C₁₈H₂₂N₂O₃S	详情	详情
(VII)	23627	(2S)-2-[(4-morpholinylcarbonyl)amino]-3-phenylpropionic acid	C₁₄H₁₈N₂O₄	详情	详情

Extended Information