【结 构 式】 |
【药物名称】 【化学名称】6-Methylthieno[3,4-c]pyridin-4(5H)-one 【CA登记号】 【 分 子 式 】C8H7NOS 【 分 子 量 】165.21509 |
【开发单位】University of Bath (Originator) 【药理作用】ONCOLYTIC DRUGS, Radiation Therapy, Radiosensitizers, NAD+ ADP-Ribosyltransferase (poly(ADP-ribose)polymerase; PARP) Inhibitors |
合成路线1
The intermediate 4-bromothiophene-3-carboxylic acid (II) was prepared in low yield by lithium-halogen exchange of 3,4-dibromothiophene (I) with n-BuLi in Et2O at -78 C, followed by quenching with solid CO2. Alternatively, lithiation of (I) at -116 C and further quenching with ethyl chloroformate provided ethyl ester (III) in moderate yields, accompanied by some byproducts that were separated by column chromatography. The required carboxylic acid (II) was then formed by saponification of (III) with NaOH. Subsequent condensation of bromoacid (II) with acetylacetone (IV) in the presence of potassium tert-butoxide and copper powder in refluxing tert-butanol provided the thienylpentanedione (V). Deacetylation with aqueous ammonia then gave the monoketone (VI). The target thienopyridinone was finally obtained by cyclization of (VI) with ammonium acetate in refluxing AcOH.
【1】 Shinkwin, A.E.; et al.; Synthesis of thiophenecarboxamides, thieno[3,4-c]p. Bioorg Med Chem 1999, 7, 2, 297. |
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) | 23826 | 3,4-dibromothiophene | 3141-26-2 | C4H2Br2S | 详情 | 详情 |
(II) | 11620 | 2,4-Pentanedione;acetylacetone | 123-54-6 | C5H8O2 | 详情 | 详情 |
(II) | 23827 | 4-bromo-3-thiophenecarboxylic acid | C5H3BrO2S | 详情 | 详情 | |
(III) | 23828 | ethyl 4-bromo-3-thiophenecarboxylate | C7H7BrO2S | 详情 | 详情 | |
(V) | 23832 | 4-[(Z)-1-acetyl-2-hydroxy-1-propenyl]-3-thiophenecarboxylic acid | C10H10O4S | 详情 | 详情 | |
(VI) | 23833 | 4-(2-oxopropyl)-3-thiophenecarboxylic acid | C8H8O3S | 详情 | 详情 |