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【结 构 式】 
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【分子编号】15454 【品名】4-(2,2-dimethylpropanoyl)benzoyl chloride 【CA登记号】 |
【 分 子 式 】C12H13ClO2 【 分 子 量 】224.68672 【元素组成】C 64.15% H 5.83% Cl 15.78% O 14.24% |
合成路线1
该中间体在本合成路线中的序号：(II)The reaction of 4-(pivaloyl)benzoic acid (I) with refluxing SOCl2 gives the corresponding acyl chloride (II), which is condensed with methoxyamine (III) by means of NaOH in THF to yield N-methoxy-4-(pivaloyl)benzamide (IV). Finally, this compound is condensed with more acyl chloride (II) by means of triethylamine in toluene.
| 【1】 Mealy, N.; Castaner, J.; SDZ-FOX-988. Drugs Fut 1996, 21, 3, 258. |
| 【2】 Kapa, P.K.; Lee, G.T.-S.; Nadelson, J.; Simpson, W.R.J.; Sunay, U.B. (Novartis AG; Novartis Deutschland GmbH); N-Oxymidic acid derivs. EP 0463989; JP 1992230255 . |
| 【3】 Lee, G.T.; Sunay, U.B.; Kapa, P.K. (Novartis AG); Process for preparing substd. N-oxy-imidic acid derivs. US 5319123 . |
| 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) | 15453 | 4-(2,2-dimethylpropanoyl)benzoic acid | C12H14O3 | 详情 | 详情 | |
| (II) | 15454 | 4-(2,2-dimethylpropanoyl)benzoyl chloride | C12H13ClO2 | 详情 | 详情 | |
| (III) | 15455 | (aminooxy)methane; O-methylhydroxylamine | 67-62-9 | CH5NO | 详情 | 详情 |
| (IV) | 15456 | 4-(2,2-dimethylpropanoyl)-N-methoxybenzamide | C13H17NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Radiolabeled SDZ-FOX-988 has been synthesized as follows: The condensation of 4-bromotoluene (I) with [14C]-cuprous cyanide in DMSO at 180 C gives the labeled 4-methylbenzonitrile (II), which by a Grignard reaction with tert-butylmagnesium chloride in THF yields the ketone (IV). The oxidation of (IV) with KMnO4 in tert-butanol affords the labeled 4-pivaloylbenzoic acid (V), which by reaction with refluxing SOCl2 gives the corresponding acyl chloride (VI). The reaction of (VI) with methoxyamine (VII) and triethylamine in toluene yields the corresponding amide (VIII), which is finally condensed with more acyl chloride (VI), by means of triethylamine in toluene.
| 【1】 Sunay, U.B.; Talbot, K.; Prasad, K.; Lee, G.; Jones, L.; Synthesis of [14C2]SDZ FOX 988, a hypoglycemic agent. J Label Compd Radiopharm 1995, 36, 6, 529-35. |
| 【2】 Mealy, N.; Castaner, J.; SDZ-FOX-988. Drugs Fut 1996, 21, 3, 258. |
| 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) | 14044 | 4-Bromotoluene; 1-Bromo-4-methylbenzene | 106-38-7 | C7H7Br | 详情 | 详情 |
| (II) | 15458 | 4-methylbenzonitrile; p-tolunitrile | 104-85-8 | C8H7N | 详情 | 详情 |
| (II) | 45171 | 4-methylbenzonitrile | C8H7N | 详情 | 详情 | |
| (III) | 15459 | tert-butyl(chloro)magnesium | 677-22-5 | C4H9ClMg | 详情 | 详情 |
| (IV) | 15460 | 2,2-dimethyl-1-(4-methylphenyl)-1-propanone; 2,2,4'-TRIMETHYLPROPIOPHENONE | 30314-44-4 | C12H16O | 详情 | 详情 |
| (IV) | 45250 | 2,2-dimethyl-1-(4-methylphenyl)-1-propanone | C12H16O | 详情 | 详情 | |
| (V) | 15453 | 4-(2,2-dimethylpropanoyl)benzoic acid | C12H14O3 | 详情 | 详情 | |
| (V) | 45251 | 4-(2,2-dimethylpropanoyl)benzoic acid | C12H14O3 | 详情 | 详情 | |
| (VI) | 15454 | 4-(2,2-dimethylpropanoyl)benzoyl chloride | C12H13ClO2 | 详情 | 详情 | |
| (VI) | 45252 | 4-(2,2-dimethylpropanoyl)benzoyl chloride | C12H13ClO2 | 详情 | 详情 | |
| (VII) | 15456 | 4-(2,2-dimethylpropanoyl)-N-methoxybenzamide | C13H17NO3 | 详情 | 详情 | |
| (VIII) | 15455 | (aminooxy)methane; O-methylhydroxylamine | 67-62-9 | CH5NO | 详情 | 详情 |
| (VIII) | 45253 | 4-(2,2-dimethylpropanoyl)-N-methoxybenzamide | C13H17NO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)Treatment of 4-(2,2-dimethyl-1-oxopropyl)benzoic acid (I) with thionyl chloride afforded the corresponding acid chloride (II). The title triester was then obtained by acylation of 2-(hydroxymethyl)-1,4-butanediol (IV) with acid chloride (II) in the presence of DMAP or Et3N. The triol (IV) has been obtained by reduction of ethane-1,1,2-tricarboxylic acid triethyl ester (III) with LiAlH4 under standard conditions.
| 【1】 Otero, D.A.; Bebernitz, G.R.; Dain, J.G.; Strohschein, R.J.; Deems, R.O.; Simpson, W.R.; Reduction in glucose levels in STZ diabetic rats by 4-(2,2-dimethyl-1-oxopropyl)benzoic acid: A prodrug approach for targeting the liver. J Med Chem 2001, 44, 4, 512. |