N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide -Drug Synthesis Database

【结构式】

【分子编号】59947

【品名】N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide

【CA登记号】

【分子式】C₁₄H₁₈N₂O₂

【分子量】246.3092

【元素组成】C 68.27% H 7.37% N 11.37% O 12.99%

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：(IX)

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2

该中间体在本合成路线中的序号：(X)

Bromination of 5-aminopyrazole (XI) with Br2 in AcOH gives 4-bromo-5-aminopyrazole (XII), which is cyclized with N-[3-[3-(dimethylamino)-2-propenoyl]phen-yl]-N-methylacetamide (X) in AcOH to yield the 3-bromo-pyrazolo[1,5-a]pyrimidine derivative (XIII). Finally, this compound can be condensed with either 2-thienylcarbonyl chloride (XIV) by means of Zn or Mg or with 2-thienylboronic acid (XV) and CO by means of a Pd(0) catalyst.

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
(X)	59947	N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide		C₁₄H₁₈N₂O₂	详情	详情
(XI)	56012	1H-pyrazol-5-amine; 1H-pyrazol-5-ylamine	916420-28-5	C₃H₅N₃	详情	详情
(XII)	62961	4-bromo-1H-pyrazol-5-ylamine; 4-bromo-1H-pyrazol-5-amine		C₃H₄BrN₃	详情	详情
(XIII)	62962	N-[3-(3-bromopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide		C₁₅H₁₃BrN₄O	详情	详情
(XIV)	14103	2-Thiophenecarbonyl chloride	5271-67-0	C₅H₃ClOS	详情	详情
(XV)	62963	2-thiophenylboronic acid		C₄H₅BO₂S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

Cyclization of 2-aminopyrazole (XI) with the acetamide (X) in AcOH gives the pyrazolo[1,5-a]pyrimidine derivative (XVI), which is finally acylated with 2-thienylcarbonyl chloride (XIV) by means of AlCl3.

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
(X)	59947	N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide		C₁₄H₁₈N₂O₂	详情	详情
(XI)	56012	1H-pyrazol-5-amine; 1H-pyrazol-5-ylamine	916420-28-5	C₃H₅N₃	详情	详情
(XIV)	14103	2-Thiophenecarbonyl chloride	5271-67-0	C₅H₃ClOS	详情	详情
(XVI)	62964	N-methyl-N-(3-pyrazolo[1,5-a]pyrimidin-7-ylphenyl)acetamide		C₁₅H₁₄N₄O	详情	详情

合成路线4

该中间体在本合成路线中的序号：(X)

Cyclization of ethoxymethylenemalonodinitrile (XVII) with hydrazine gives 5-aminopyrazole-4-carbonitrile (XVIII), which is further cyclized with acetamide (X) in refluxing AcOH to yield the 3-cyanopyrazolo[1,5-a]pyrimidine derivative (XIX). Finally, this compound is condensed with 2-bromothiophene (XX) by means of Mg.

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
(X)	59947	N-{3-[(E)-3-(dimethylamino)-2-propenoyl]phenyl}-N-methylacetamide		C₁₄H₁₈N₂O₂	详情	详情
(XVII)	13017	Ethoxymethylenemalononitrile; 2-(Ethoxymethylene)malononitrile	123-06-8	C₆H₆N₂O	详情	详情
(XVIII)	57051	5-Amino-4-pyrazolecarbonitrile		C₄H₄N₄	详情	详情
(XIX)	62965	N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-methylacetamide		C₁₆H₁₃N₅O	详情	详情
(XX)	13681	2-Bromothiophene	1003-09-4	C₄H₃BrS	详情	详情

合成路线5

该中间体在本合成路线中的序号：(X)

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

Extended Information