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【结 构 式】

【分子编号】63459

【品名】5-isothiazolecarbaldehyde

【CA登记号】

【 分 子 式 】C4H3NOS

【 分 子 量 】113.13996

【元素组成】C 42.46% H 2.67% N 12.38% O 14.14% S 28.34%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(V)

Propargyl alcohol (I) is oxidized with CrO3 under reduced pressure to give propynal (II), which is treated with sodium thiosulfate to afford the aldehyde dithionite (III). Subsequent cyclization of (III) in liquid ammonia gives rise to isothiazole (IV). The lithiated derivative of (IV) is formylated by means of DMF to provide aldehyde (V), which is further reduced to alcohol (VI) employing NaBH4 in THF (1). Bromination of alcohol (VI) in the presence of CBr4/PPh3 leads to 5-bromomethylisothiazole (VII). This is then converted into the phosphonium salt (VIII) upon treatment with triphenylphosphine in refluxing acetonitrile. Wittig condensation of (VIII) with the formyl pyrrolidine (IX) produces the ethenylpyrrolidine derivative (X). The mesylate group of (X) is displaced with potassium thioacetate to produce thioester (XI), which is subsequently hydrolyzed to thiol (XII) with methanolic NaOH. Condensation of thiol (XII) with the enol phosphate (XIII) in the presence of diisopropylethylamine affords the protected carbapenem derivative (XIV). This is finally deprotected with Bu3SnH and palladium catalyst to furnish the title compound (1,2)

1 Kang, Y.-K.; Lee, K.-S.; Yoo, K.-H.; Shin, K.-J.; Kim, D.-C.; Lee, C.-S.; Kong, J.Y.; Kim, D.J.; Synthesis and biological evaluation of novel 1beta-methylcarbapenems with isothiazoloethenyl side chains. Bioorg Med Chem Lett 2003, 13, 3, 463.
2 Kim, D.J.; Yoo, K.H.; Kang, Y.K.; Park, S.W.; Shin, K.J.; Seo, K.J. (Korea Institute of Science and Technology); Novel 1beta-methylcarbapenem derivs. and process for preparation thereof. WO 0202561 .
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) 16664 Propargyl Alcohol; 2-propyn-1-ol 107-19-7 C3H4O 详情 详情
(II) 23544 propiolaldehyde C3H2O 详情 详情
(III) 63457 sodium 1-{[oxido(dioxo)-lambda~6~-sulfanyl]sulfanyl}-3-oxo-1-propene C3H3NaO4S2 详情 详情
(IV) 63458 isothiazole C3H3NS 详情 详情
(V) 63459 5-isothiazolecarbaldehyde C4H3NOS 详情 详情
(VI) 63460 5-isothiazolylmethanol C4H5NOS 详情 详情
(VII) 63461 5-(bromomethyl)isothiazole C4H4BrNS 详情 详情
(VIII) 63462 (5-isothiazolylmethyl)(triphenyl)phosphonium bromide C22H19BrNPS 详情 详情
(IX) 49446 allyl (2S,4R)-2-formyl-4-[(methylsulfonyl)oxy]-1-pyrrolidinecarboxylate C10H15NO6S 详情 详情
(X) 63463 2-propenyl 2-[2-(5-isothiazolyl)ethenyl]-4-[(methylsulfonyl)oxy]-1-pyrrolidinecarboxylate C14H18N2O5S2 详情 详情
(XI) 63464 2-propenyl 4-(acetylsulfanyl)-2-[2-(5-isothiazolyl)ethenyl]-1-pyrrolidinecarboxylate C15H18N2O3S2 详情 详情
(XII) 63465 2-propenyl 2-[2-(5-isothiazolyl)ethenyl]-4-sulfanyl-1-pyrrolidinecarboxylate C13H16N2O2S2 详情 详情
(XIII) 32617 allyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate C25H26NO8P 详情 详情
(XIV) 63466 2-propenyl 6-(1-hydroxyethyl)-3-({5-[2-(5-isothiazolyl)ethenyl]-1-[(2-propenyloxy)carbonyl]-3-pyrrolidinyl}sulfanyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate C26H31N3O6S2 详情 详情
Extended Information