3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide -Drug Synthesis Database

【结构式】

【分子编号】11983

【品名】3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide

【CA登记号】7463-31-2

【分子式】C₁₀H₁₁NO₂

【分子量】177.20288

【元素组成】C 67.78% H 6.26% N 7.9% O 18.06%

与该中间体有关的原料药合成路线共 5 条

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1

该中间体在本合成路线中的序号：(I)

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

合成目标

【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：(VII)

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.

参考文献中间体

合成目标

【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：(VIII)

Reaction of 3-(acetamido)acetophenone (VIII) with iodomethane and NaH gives 3-(N-methylacetamido)acetophenone (XXVIII), which is mixed with 3-oxo-3-(2-thienyl)propionitrile (VII) and treated with dimethylformamide dimethylacetal to yield a mixture of the dimethylaminomethylene derivatives (IV) and (X). This mixture, without isolation, is cyclized with aminoguanidine (V) by treatment first with NaOH in ethanol and then with refluxing AcOH.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castaner, J.; Martin, L.; Indiplon. Drugs Fut 2003, 28, 8, 739.
【2】 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
(IV)	59945	(E)-3-(dimethylamino)-2-(2-thienylcarbonyl)-2-propenenitrile		C₁₀H₁₀N₂OS	详情	详情
(V)	10015	1-Hydrazinecarboximidamide; Hydrazinecarboximidamide	79-17-4	CH₆N₄	详情	详情
(VII)	62972	3-oxo-3-(2-thienyl)propanenitrile		C₇H₅NOS	详情	详情
(VIII)	11983	3'-Acetamidoacetophane; m-Acetamidoacetophenone; N-(3-Acetylphenyl)acetamide	7463-31-2	C₁₀H₁₁NO₂	详情	详情
(X)	59947	N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide		C₁₄H₁₈N₂O₂	详情	详情
(XXVIII)	62971	N-(3-acetylphenyl)-N-methylacetamide		C₁₁H₁₃NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【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

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【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