【结 构 式】 ![]() |
【药物名称】Tiopinac 【化学名称】2-(11-Oxo-6,11-dihydrodibenzo[b,e]thiepin-3-yl)acetic acid 【CA登记号】61220-69-7 【 分 子 式 】C16H12O3S 【 分 子 量 】284.33624 |
【开发单位】 【药理作用】 |
合成路线1
The esterification of 2-nitroterephthalic acid (I) with isopropanol by means of dry HCl gives the corresponding dusoproyl ester (II), which by reaction with benzylmercaptane by means of NaH in DMF yields diisopropyl 2-benzylthioterephthalate (III). This compound is hydrolyzed with KOH in refluxing methanol affording the correspon-ding acid (IV), which is converted into its diacid chloride (V) by treatment with refluxing SOCl2. The cyclization of (V) with AlCl3 in methylene chloride - nitromethane affords 6,11-dihydrodibenzo[b]thiepin-11-one-3-carbonyl chloride (VI), which is treated with diazomethane in ether - methylene chloride to yield the 3-diazoacetyl derivative (VII). The Arndt-Eister reaction of (VII) with silver benzoate in refluxing methanol affords methyl 6,11-dihydrodibenzo[b,e]thiepin-11-one-3-acetate (VIII), which is finally hydrolyzed with KOH in refluxing methanol.
【1】 Castañer, J.; Leeson, P.; Tiopinac. Drugs Fut 1978, 3, 12, 896. |
【2】 Ackrell, J. (Syntex (USA), Inc.); 6,11-Dihydrodibenzothiepin-11-ones, compositions and uses thereof. US 4000308 . |
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) | 39919 | 2-nitroterephthalic acid | 610-29-7 | C8H5NO6 | 详情 | 详情 |
(II) | 39920 | diisopropyl 2-nitroterephthalate | C14H17NO6 | 详情 | 详情 | |
(III) | 21110 | benzylhydrosulfide; phenylmethanethiol | 100-53-8 | C7H8S | 详情 | 详情 |
(IV) | 39921 | diisopropyl 2-(benzylsulfanyl)terephthalate | C21H24O4S | 详情 | 详情 | |
(V) | 39922 | 2-(benzylsulfanyl)terephthalic acid | C15H12O4S | 详情 | 详情 | |
(VI) | 39923 | 3-(benzylsulfanyl)benzoyl chloride | C14H11ClOS | 详情 | 详情 | |
(VII) | 39924 | 11-oxo-6,11-dihydrodibenzo[b,e]thiepine-3-carbonyl chloride | C15H9ClO2S | 详情 | 详情 | |
(VIII) | 39925 | 3-(2-diazoacetyl)dibenzo[b,e]thiepin-11(6H)-one | C16H10N2O2S | 详情 | 详情 | |
(IX) | 39926 | methyl 2-(11-oxo-6,11-dihydrodibenzo[b,e]thiepin-3-yl)acetate | C17H14O3S | 详情 | 详情 |