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【结 构 式】 
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【分子编号】11985 【品名】N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]acetamide 【CA登记号】 |
【 分 子 式 】C13H16N2O2 【 分 子 量 】232.28232 【元素组成】C 67.22% H 6.94% N 12.06% O 13.78% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of N-(3-acetylphenyl)acetamide (I) with dimethylformamide dimethylacetal (II) at reflux temperature gives N-[3-[3-(dimethylamino)-2-propenoyl]phenyl]acetamide (III), which is alkylated with NaH and ethyl iodide to the corresponding N-ethyl derivative (IV). Finally, this compound is cyclized with 3-aminopyrazole-4-carbonitrile (V) in refluxing acetic acid.
| 【1】 Mealy, N.; Castaner, J.; Zaleplon. Drugs Fut 1996, 21, 1, 37. |
| 【2】 Dusza, J.P.; Tomcufcik, A.S.; Albright, J.D. (American Cyanamid Co.); [7-(3-Disubstd. amino)phenyl]pyrazolo[1,5-a]pyrimidines. EP 0208846; JP 1986260083; JP 1995084468; US 4626538 . |
| 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) | 11983 | 3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide | 7463-31-2 | C10H11NO2 | 详情 | 详情 |
| (II) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (III) | 11985 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]acetamide | C13H16N2O2 | 详情 | 详情 | |
| (IV) | 11986 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]-N-ethylacetamide | C15H20N2O2 | 详情 | 详情 | |
| (V) | 11987 | 3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole | 16617-46-2 | C4H4N4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)3-(Acetamido)acetophenone (VII) was converted to enaminone (VIII) upon condensation with dimethylformamide dimethylacetal. The amide N of (VIII) was then alkylated by means of iodomethane and NaH or, alternatively, under phase-transfer conditions to give (IX). Finally, condensation between enaminone (IX) and aminopyrazole (VI) in refluxing AcOH provided the target pyrazolopyrimidine.
| 【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739. |
| 【2】 Dusza, J.P.; Tomcufcik, A.S.; Albright, J.D. (Wyeth); Aryl and heteroaryl 7-(aryl and heteroaryl)-pyrazolo[1,5-a]pyrimidin-3-ylmethanones. DE 3422844; EP 0129847; JP 1985019788 . |
| 【3】 Tomcufcik, A.S.; Dusza, J.P.; Albright, J.D.; Beer, B. (Wyeth); N-Methyl-N-(-[3-[-2-thienylcarbonyl]-pyrazol-[1,5-alpha]-pyrimidin-7-yl]phenyl)acetamide and compsns. and methods related thereto. US 6399621 . |
| 【4】 Wilcoxen, K.M.; Gross, R.S. (Neurocrine Biosciences Inc.); Synthesis of substd. pyrazolopyrimidines. WO 0110868 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 59946 | (3-amino-1H-pyrazol-4-yl)(2-thienyl)methanone | C8H7N3OS | 详情 | 详情 | |
| (VII) | 11983 | 3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide | 7463-31-2 | C10H11NO2 | 详情 | 详情 |
| (VIII) | 11985 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]acetamide | C13H16N2O2 | 详情 | 详情 | |
| (IX) | 59947 | N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide | C14H18N2O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)
| 【1】 Shen JS，Li JF，Li FW，et al. 2002．Synthesis of zaleplon.中国医药工业杂卷．33(7): 313～314 |
| 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) | 49701 | Acetic anhydride; Acetyl oxide | 108-24-7 | C4H6O3 | 详情 | 详情 |
| (II) | 66972 | 3-Aminoacetophenone;3-Amino acetophenone;m-Aminoacetophenone;1-(3-Aminophenyl)ethanone | 99-03-6 | C8H9NO | 详情 | 详情 |
| (III) | 11983 | 3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide | 7463-31-2 | C10H11NO2 | 详情 | 详情 |
| (IV) | 11985 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]acetamide | C13H16N2O2 | 详情 | 详情 | |
| (V) | 11986 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]-N-ethylacetamide | C15H20N2O2 | 详情 | 详情 | |
| (VI) | 11987 | 3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole | 16617-46-2 | C4H4N4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(V)
| 【1】 Zheng LY, Wang SQ, Li BC, et aL. 2001.Improvement on the synthetic technology of zaleplon as a new sedative and hypnoticdrug. 中国药物化学杂志，11 (6)：353～355 |
| 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) | 10317 | Acetophenone | 98-86-2 | C8H8O | 详情 | 详情 |
| (II) | 61934 | 1-(3-nitrophenyl)-1-ethanone；3-Nitroacetophenone;m-Nitroacetophenone | 121-89-1 | C8H7NO3 | 详情 | 详情 |
| (III) | 66972 | 3-Aminoacetophenone;3-Amino acetophenone;m-Aminoacetophenone;1-(3-Aminophenyl)ethanone | 99-03-6 | C8H9NO | 详情 | 详情 |
| (IV) | 11983 | 3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide | 7463-31-2 | C10H11NO2 | 详情 | 详情 |
| (V) | 11985 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]acetamide | C13H16N2O2 | 详情 | 详情 | |
| (VI) | 11986 | N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]-N-ethylacetamide | C15H20N2O2 | 详情 | 详情 | |
| (VII) | 11987 | 3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole | 16617-46-2 | C4H4N4 | 详情 | 详情 |