Zaleplon, LJC-10846, L-846, CL-284846, Zerene, Sonata, -Drug Synthesis Database

【结构式】

【药物名称】Zaleplon, LJC-10846, L-846, CL-284846, Zerene, Sonata

【化学名称】3'-(3-Cyanopyrazolo[1,5-a]pyrimidin-7-yl)-N-ethylacetanilide
　　　　　　N-[3-(3-Cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide

【CA登记号】151319-34-5

【分子式】C₁₇H₁₅N₅O

【分子量】305.342

【开发单位】King Pharmaceuticals (Proprietary), Wyeth Pharmaceuticals (Originator), Lundbeck (Licensee)

【药理作用】PSYCHOPHARMACOLOGIC DRUGS, Sedative/Hypnotics, Sleep Disorders, Treatment of, GABA(A) BZ Site Receptor Agonists

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6

合成路线1

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.

参考文献中间体

【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

参考文献中间体

【1】 Khamar BM, Modi IA, Shukla MC, et aL. 2006. A process for the preparation of zaleplon. W0 2006070244

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)	16602	ethyl formate	109-94-4	C₃H₆O₂	详情	详情
(II)	66968	1-(3-bromophenyl)ethanone	2142-63-4	C₈H₇BrO	详情	详情
(III)	66969	sodium 1-(3-bromophenyl)-1,3-dioxopropan-2-ide		C₉H₆BrNaO₂	详情	详情
(IV)	11987	3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole	16617-46-2	C₄H₄N₄	详情	详情
(V)	66970	7-(3-bromophenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile	933054-30-9	C₁₃H₇BrN₄	详情	详情
(VI)	66971	N-(3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl)acetamide	115931-01-6	C₁₅H₁₁N₅O	详情	详情

合成路线3

参考文献中间体

【1】 Koradi F. Feher F. Magyar E, Singer C. 2005. Preparation of N-[3-(3-cyanopyrazolo [1,5-a] pyrimidin-5-yl) phenyll-N-ethylacetamide, regioisamer of Zaleplon, and crystalline forms of Zaleplon. US 2005032818
【2】 Kankan RN, Rao DR. 2005. Zaleplon Synthesis, W0 2005023813
【3】 Korycinska M, Stawinski T, Wieczorek M. 2003. A process for the preparation of zaleplon via the cyclocondensation reaction of 3-dimethylamino-l-(3-N-ethyl-N-aoetylaminophenyl) -2-propen-l-one with 3- aminopyrazole-4-carborutrile in an aqueous solution of formic acid. W0 2003095456
【4】 Subramanian RS, Sathyanarayanan N, Janardhana PNR, et aL. 2005. Process for prepantion of N-[3-(3- cyanopynzolo [1,5-a] pyrimidin-7-yl) phenyl]-n-ethylacetamide. W0 2005099712

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)	11987	3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole	16617-46-2	C₄H₄N₄	详情	详情
(II)	11986	N-[3-[(E)-3-(Dimethylamino)-2-propenoyl]phenyl]-N-ethylacetamide		C₁₅H₂₀N₂O₂	详情	详情

合成路线4

参考文献中间体

【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5

参考文献中间体

【1】 Horns S. 2003. Method for producing N-ethyl-N-[3-(3-cyanopyrazolo [1, 5α] pyrimidin-7-yl) phenyl] acetamide (zaleplon). W0 2003068775

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)	16602	ethyl formate	109-94-4	C₃H₆O₂	详情	详情
(II)	66973	N-(3-acetylphenyl)-N-ethylacetamide		C₁₂H₁₅NO₂	详情	详情
(III)	66974	sodium 1-(3-(N-ethylacetamido)phenyl)-1,3-dioxopropan-2-ide		C₁₃H₁₄NaNO₃	详情	详情
(IV)	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6

参考文献中间体

【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

Extended Information

Drug NewChemical Entity Original Patent(1)