7-iodoimidazo[5,1-b][1,3]thiazole -Drug Synthesis Database

【结构式】

【分子编号】47193

【品名】7-iodoimidazo[5,1-b][1,3]thiazole

【CA登记号】

【分子式】C₅H₃IN₂S

【分子量】250.06277

【元素组成】C 24.02% H 1.21% I 50.75% N 11.2% S 12.82%

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：(I)

Imidazothiazole (I) is converted into methylsulfanyl derivative (II) by first reaction with EtMgBr in THF followed by treatment with MeSSO2Me. Lithiation of derivative (II) by means of BuLi in THF/hexane, followed by reaction with tributyltin chloride and LiHMDS, provides tributyltin derivative (III), which is then condensed with carbapenem derivative (VI) by means of Pd(dba)3, P(2-furyl)3 and ZnCl2 in NMP to afford (VII). (Derivative (VI) in turn can be obtained by first cyclization of the diazo compound (IV) by means of ZnBr2 and Rh2Oct4 in MeOAc/THF to provide bicyclic ketoester (V), which is finally treated with triflic anhydride (Tf2O) and DIEA in acetonitrile. The target product is finally obtained by first N-alkylation of the imidazothiazole ring of (VII) with iodoacetamide (VIII) in acetonitrile followed by deprotection of the carboxylic acid by hydrogenation over Pd/C inTHF/H2O.

参考文献中间体

合成目标

【2】 Lynch, J.E.; Liu, T.M.-H.; Volante, R.P. (Merck & Co., Inc.); Process for synthesizing carbapenem intermediates using a rhodium catalyst and Lewis acid. US 5493018 .
【1】 Sakakibara, S.; Takata, T.; Yamamoto, K.; Shitara, E.; Shibasaki, Y.; Shimizu, A.; Komiya, I.; CP5068, a new carbapenem: Synthesis and structure-activity relationships. 40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000, Toronto) 2000, Abst F-1236.

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)	47193	7-iodoimidazo[5,1-b][1,3]thiazole		C₅H₃IN₂S	详情	详情
(II)	47194	7-(methylsulfanyl)imidazo[5,1-b][1,3]thiazole; imidazo[5,1-b][1,3]thiazol-7-yl methyl sulfide		C₆H₆N₂S₂	详情	详情
(III)	47195	7-(methylsulfanyl)-2-(tributylstannyl)imidazo[5,1-b][1,3]thiazole; methyl 2-(tributylstannyl)imidazo[5,1-b][1,3]thiazol-7-yl sulfide		C₁₈H₃₂N₂S₂Sn	详情	详情
(IV)	38749	4-nitrobenzyl (4R)-2-diazo-4-[(2R,3S)-3-[(1R)-1-hydroxyethyl]-4-oxoazetidinyl]-3-oxopentanoate		C₁₇H₁₈N₄O₇	详情	详情
(V)	22575	4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate		C₁₇H₁₈N₂O₇	详情	详情
(VI)	38750	4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(trifluoromethyl)sulfonyl]oxy]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₁₈H₁₇F₃N₂O₉S	详情	详情
(VII)	47196	4-nitrobenzyl (4S,5R)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[7-(methylsulfanyl)imidazo[5,1-b][1,3]thiazol-2-yl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₃H₂₂N₄O₆S₂	详情	详情
(VIII)	47197	2-iodoacetamide	144-48-9	C₂H₄INO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Metalation of 7-iodoimidazo[5,1-b]thiazole (I) with ethylmagnesium bromide, followed by addition to 3-pyridinecarboxaldehyde (II) provides carbinol (III), which is further oxidized to ketone (IV) by means of MnO2. Lithiation of (IV) and further treatment with chlorotributyltin affords the stannyl derivative (V). The carbapenem ketone (VI) is converted into the vinyl triflate (VII) upon treatment with trifluoromethanesulfonic anhydride and diisopropyl ethylamine. Then, Stille coupling between vinyl triflate (VII) and the stannyl derivative (V) gives rise to the imidazothiazolyl carbapenem (VIII). Quaternization of the pyridine ring of (VIII) with iodoacetamide furnishes the pyridinium salt (IX). Finally the p-nitrobenzyl ester group of (IX) is removed by hydrogenolysis over Pd/C to provide the title compound

参考文献中间体

合成目标

【1】 Shitara, E.; Yamamoto, Y.; Kano, Y.; Maruyama, T.; Takahashi, M.; Atsumi, K.; CP5609, a novel parenteral carbapenem: Synthesis and structure-activity relationships. 42nd Intersci Conf Antimicrob Agents Chemother (Sept 27 2002, San Diego) 2002, Abst F-319.

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)	47193	7-iodoimidazo[5,1-b][1,3]thiazole		C₅H₃IN₂S	详情	详情
(II)	12849	Nicotinaldehyde; 3-Pyridinecarboxaldehyde	500-22-1	C₆H₅NO	详情	详情
(III)	62675	imidazo[5,1-b][1,3]thiazol-7-yl(3-pyridinyl)methanol		C₁₁H₉N₃OS	详情	详情
(IV)	62676	imidazo[5,1-b][1,3]thiazol-7-yl(3-pyridinyl)methanone		C₁₁H₇N₃OS	详情	详情
(V)	62677	3-pyridinyl[2-(tributylstannyl)imidazo[5,1-b][1,3]thiazol-7-yl]methanone		C₂₃H₃₃N₃OSSn	详情	详情
(VI)	22575	4-nitrobenzyl (2R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate		C₁₇H₁₈N₂O₇	详情	详情
(VII)	38750	4-nitrobenzyl (4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(trifluoromethyl)sulfonyl]oxy]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₁₈H₁₇F₃N₂O₉S	详情	详情
(VIII)	62678	4-nitrobenzyl (4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[7-(3-pyridinylcarbonyl)imidazo[5,1-b][1,3]thiazol-2-yl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate		C₂₈H₂₃N₅O₇S	详情	详情
(IX)	62679	1-(2-amino-2-oxoethyl)-3-{[2-((4S,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-{[(4-nitrobenzyl)oxy]carbonyl}-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl)imidazo[5,1-b][1,3]thiazol-7-yl]carbonyl}pyridinium iodide		C₃₀H₂₇IN₆O₈S	详情	详情

Extended Information