6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione -Drug Synthesis Database

【结构式】

【分子编号】30125

【品名】6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione

【CA登记号】

【分子式】C₁₈H₂₅NO₃SSi

【分子量】363.55294

【元素组成】C 59.47% H 6.93% N 3.85% O 13.2% S 8.82% Si 7.73%

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：(VIIIb)

Chlorosulfonylation of 1-methylnaphthalene (I) produced the sulfonyl chloride (II), which was converted to sulfonamide (III) upon treatment with diethylamine. Nitration of (III) produced nitro compound (IV), which was reductively cyclized to the naphthosultam (V). Carboxylation at the methyl group of (V) by means of CO2 and LDA afforded carboxylic acid (VI), and further reduction of (VI) with NaBH4 and BF3-Et2O gave alcohol (VII). Silylation of (VII) with either N,O-bistrimethylsilylacetamide or triethylsilyl chloride and imidazole produced the respective silyl ethers (VIIa) and (VIIb).

参考文献中间体

合成目标

【1】 Wilkening, R.R.; Wildonger, K.J.; Ratcliffe, R.W.; et al.; Synthesis and evaluation of anti-MRSA 1beta-methyl-2-(naphthosultamyl) methyl-carbapenems: Discovery of L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-32.
【2】 Yasuda, N.; et al.; Preparation of anti-MRS carbapenem L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-31.
【3】 Wilkening, R.R.; Ratcliffe, R.W.; Blizzard, T.A. (Merck & Co., Inc.); Carbapenem antibacterial cpds., compsns. containing such cpds. and methods of treatment. EP 0906313; JP 1999508279; US 5756725; WO 9740048 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIIa)	23835	6-[3-(trimethylsilyl)propyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione; 6-[2-[(trimethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione		C₁₅H₁₉NO₃SSi	详情	详情
(VIIIb)	30125	6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione		C₁₈H₂₅NO₃SSi	详情	详情
(I)	30117	1-methylnaphthalene	90-12-0	C₁₁H₁₀	详情	详情
(II)	30118	4-methyl-1-naphthalenesulfonyl chloride		C₁₁H₉ClO₂S	详情	详情
(III)	30119	N,N-diethyl-4-methyl-1-naphthalenesulfonamide		C₁₅H₁₉NO₂S	详情	详情
(IV)	30120	N,N-diethyl-4-methyl-8-nitro-1-naphthalenesulfonamide		C₁₅H₁₈N₂O₄S	详情	详情
(V)	30121	6-methyl-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione		C₁₁H₉NO₂S	详情	详情
(VI)	30122	2-(1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl)acetic acid		C₁₂H₉NO₄S	详情	详情
(VII)	30123	6-(2-hydroxyethyl)-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione		C₁₂H₁₁NO₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIIIb)

Coupling of carbapenem (XLII) with sultam (VIIIb) under Mitsunobu conditions gave adduct (XLVII), which was desylilated to yield alcohol (XLVIII). Formation of the corresponding triflate, followed by condensation with bicyclic compound (XLV) provided (II), which was converted to (L) upon treatment with HCl and NaCl. The p-nitrobenzyl ester of (L) was finally deprotected by hydrogenation over Pd/C to provide the title carboxylic acid. A further procedure to obtain the target compound is to repeat the described synthesis but using carbapenem (XXXVII), instead of carbapenem (XLII).

参考文献中间体

合成目标

【1】 Yasuda, N.; et al.; Preparation of anti-MRS carbapenem L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-31.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIIIb)	30125	6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₁₈H₂₅NO₃SSi	详情	详情
(IL)	30160	1-(2-amino-2-oxoethyl)-4-(2-[2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl)-1,4-diazonia	C₄₆H₅₈F₆N₆O₁₅S₃Si	详情	详情
(XLII)	30154	(4S,5R,6S)-3-(hydroxymethyl)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-7-one	C₂₄H₃₄N₂O₇Si	详情	详情
(XLV)	30156	1-(2-amino-2-oxoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane trifluoromethanesulfonate	C₉H₁₆F₃N₃O₄S	详情	详情
(XLVII)	30158	2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₄₂H₅₇N₃O₉SSi₂	详情	详情
(XLVIII)	30159	6-(2-hydroxyethyl)-2-[((4S,5R,6S)-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-6-[(1R)-1-[(triethylsilyl)oxy]ethyl]-1-azabicyclo[3.2.0]hept-2-en-3-yl)methyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₃₆H₄₃N₃O₉SSi	详情	详情
(L)	30161	1-(2-amino-2-oxoethyl)-4-[2-[2-([(4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-[2-(4-nitrobenzyloxy)acetyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]methyl)-1,1-dioxo-1,2-dihydro-2H-naphtho[1,8-cd]isothiazol-6-yl]ethyl]-1,4-diazoniabicyclo[2.2.2	C₃₉H₄₄ClF₃N₆O₁₂S₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIIIb)

Condensation of azetidinone (XXIX) with sultam (VIIIb) to afford (LI), which was cyclized to the corresponding carbapenem (LII) upon refluxing in toluene. The title compound was then prepared by a sequence analogous to Scheme 25884901g.

参考文献中间体

合成目标

【1】 Wilkening, R.R.; Wildonger, K.J.; Ratcliffe, R.W.; et al.; Synthesis and evaluation of anti-MRSA 1beta-methyl-2-(naphthosultamyl) methyl-carbapenems: Discovery of L-786,392. 38th Intersci Conf Antimicrob Agents Chemother (Sept 24 1998, San Diego) 1998, Abst F-32.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIIIb)	30125	6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazole-1,1(2H)-dione	C₁₈H₂₅NO₃SSi	详情	详情
(XXIX)	30144	allyl 2-[(2R,3S)-3-((1R)-1-[[(allyloxy)carbonyl]oxy]ethyl)-2-[(1R)-3-hydroxy-1-methyl-2-oxopropyl]-4-oxoazetidinyl]-2-(triphenylphosphoranylidene)acetate	C₃₆H₃₈NO₈P	详情	详情
(LI)	30162	allyl 2-((2R,3S)-3-((1R)-1-[[(allyloxy)carbonyl]oxy]ethyl)-2-[(1R)-3-[1,1-dioxo-6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazol-2(1H)-yl]-1-methyl-2-oxopropyl]-4-oxoazetidinyl)-2-(triphenylphosphoranylidene)acetate	C₅₄H₆₁N₂O₁₀PSSi	详情	详情
(LII)	30163	allyl (4S,5R,6S)-6-((1R)-1-[[(allyloxy)carbonyl]oxy]ethyl)-3-[[1,1-dioxo-6-[2-[(triethylsilyl)oxy]ethyl]-2H-naphtho[1,8-cd]isothiazol-2(1H)-yl]methyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate	C₃₆H₄₆N₂O₉SSi	详情	详情

Extended Information