3,5-dimethyl-4-isoxazolesulfonyl chloride -Drug Synthesis Database

【结构式】

【分子编号】21618

【品名】3,5-dimethyl-4-isoxazolesulfonyl chloride

【CA登记号】80466-79-1

【分子式】C₅H₆ClNO₃S

【分子量】195.62628

【元素组成】C 30.7% H 3.09% Cl 18.12% N 7.16% O 24.54% S 16.39%

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：(II)

The sulfonation of 2(S)-amino-3-(tert-butoxycarbonylamino)propionic acid methyl ester (I) with 3,5-dimethylisoxazol-4-ylsulfonyl chloride (II) by means of triethylamine in dichloromethane gives the corresponding sulfonamide (III), which is deprotected with trifluoroacetic acid yielding the 3-aminopropionic acid derivative (IV). The condensation of (IV) with [3-(4-cyanophenyl)-4,5-dihydroisoxazol-5(R)-yl]acetic acid (V) by means of TBTU and triethylamine in DMF affords the carboxamide (VI). The cyano group of (VI) is treated first with dry HCl and then with NH3, NH4OAc, or CO3(NH4)2 to obtain the amidino group of (VII). Finally, compound (VII) is hydrolyzed with LiOH, 6N HCl, or rabbit liver esterase.

参考文献中间体

合成目标

【1】 Sielecki, T.M.; Olson, R.E.; Wityak, J.; et al.; Orally active isoxazoline glycoprotein IIb/IIIa antagonists with extended duration of action. J Med Chem 1999, 42, 7, 1178.

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)	25095	methyl (2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoate		C₉H₁₈N₂O₄	详情	详情
(II)	21618	3,5-dimethyl-4-isoxazolesulfonyl chloride	80466-79-1	C₅H₆ClNO₃S	详情	详情
(III)	25912	methyl (2S)-3-[(tert-butoxycarbonyl)amino]-2-[[(3,5-dimethyl-4-isoxazolyl)sulfonyl]amino]propanoate		C₁₄H₂₃N₃O₇S	详情	详情
(IV)	25913	methyl (2S)-3-amino-2-[[(3,5-dimethyl-4-isoxazolyl)sulfonyl]amino]propanoate		C₉H₁₅N₃O₅S	详情	详情
(V)	17555	2-[(5R)-3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetic acid		C₁₂H₁₀N₂O₃	详情	详情
(VI)	25910	methyl (2S)-3-([2-[3-(4-cyanophenyl)-4,5-dihydro-5-isoxazolyl]acetyl]amino)-2-[[(3,5-dimethyl-4-isoxazolyl)sulfonyl]amino]propanoate		C₂₁H₂₃N₅O₇S	详情	详情
(VII)	25911	methyl (2S)-3-[[2-((5R)-3-[4-[amino(imino)methyl]phenyl]-4,5-dihydro-5-isoxazolyl)acetyl]amino]-2-[[(3,5-dimethyl-4-isoxazolyl)sulfonyl]amino]propanoate		C₂₁H₂₆N₆O₇S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Friedel-Crafts acetylation of acetaminophen (I) using acetyl chloride and AlCl3 gave acetophenone (II). Subsequent condensation of (II) with N-(tert-butoxycarbonyl)-4-piperidone (III) in the presence of pyrrolidine provided the spirochroman-2,4'-piperidine (IV), from which the diamine (V) was obtained by acid hydrolysis. The piperidine amino group of (VI) was then alkylated with 1-(2-bromoethyl)naphthalene (VI) to afford (VII). Finally, condensation of the remaining amino group of (VII) with the sulfonyl chloride (VIII) furnished the title sulfonamide.

参考文献中间体

合成目标

【1】 Nerenberg, J.B.; et al.; 4-Oxospiro[benzopyran-2,4'-piperidines] as selective alpha1a-adrenergic receptor antagonists. Bioorg Med Chem Lett 1999, 9, 2, 291.

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)	21611	4'-Hydroxyacetanilide;4-Acetamidophenol;N-Acetyl-4-aminophenol;Paracetamol;Acetaminophen;p-Hydroxyacetanilide; Paracetamol; N-(4-hydroxyphenyl)acetamide	103-90-2	C₈H₉NO₂	详情	详情
(II)	21612	N-(3-acetyl-4-hydroxyphenyl)acetamide		C₁₀H₁₁NO₃	详情	详情
(III)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(IV)	21614	6-Aceatmido-4-oxo-3,4-dihydro-2H-spiro[1-benzopyran-2,4'-piperidin]-1'-ylcarboxylic acid tert-butyl ester		C₂₀H₂₆N₂O₅	详情	详情
(V)	21615	6-Amino-3,4-dihydro-2H-spiro[1-benzopyran-2,4'-piperidin]-4-one		C₁₃H₁₆N₂O₂	详情	详情
(VI)	21616	1-(2-bromoethyl)naphthalene	13686-49-2	C₁₂H₁₁Br	详情	详情
(VII)	21617	6-Amino-1'-[2-(1-naphthyl)ethyl]-3,4-dihydro-2H-spiro[1-benzopyran-2,4'-piperidin]-4-one		C₂₅H₂₆N₂O₂	详情	详情
(VIII)	21618	3,5-dimethyl-4-isoxazolesulfonyl chloride	80466-79-1	C₅H₆ClNO₃S	详情	详情

Extended Information