【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% |
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 |