2-furohydrazide -Drug Synthesis Database

【结构式】

【分子编号】41402

【品名】2-furohydrazide

【CA登记号】3326-71-4

【分子式】C₅H₆N₂O₂

【分子量】126.11492

【元素组成】C 47.62% H 4.8% N 22.21% O 25.37%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

The alkylation of 5-amino-4-cyanopyrazole (I) with n-propyl iodide led to a 4:1 inseparable mixture of regioisomers (II) and (III). This mixture was transformed into the respective imidates (IV) and (V) through refluxing in triethyl orhoformate. Subsequent addition of 2-furoic hydrazide (VI) to the nitrile group of (IV)+(V), followed by thermal cyclization in diphenyl ether at 260 C furnished the corresponding pyrazolotriazolopyrimidines. The desired regioisomer (VII) was then isolated by flash chromatography. Hydrolysis of (VII) with aqueous HCl afforded the aminopyrazole (VIII), which was further converted to the tricyclic compound (IX) by reaction with cyanamide and p-toluenesulfonic acid. Finally, coupling of (IX) with p-methoxyphenyl isocyanate (X) provided the title urea.

参考文献中间体

合成目标

【1】 Cacciari, B.; Klotz, K.-N.; Borea, P.A.; Leung, E.; Merighi, S.; Varani, K.; Gessi, S.; Spalluto, G.; Baraldi, P.G.; Ropmagnoli, R.; Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine derivatives as highly potent and selective human A3 adenosine receptor antagonists. J Med Chem 1999, 42, 22, 4473.

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)	41398	3-amino-1-propyl-1H-pyrazole-4-carbonitrile		C₇H₁₀N₄	详情	详情
(III)	41399	3-amino-2-propyl-1H-2lambda(5)-pyrazole-4-carbonitrile		C₇H₁₂N₄	详情	详情
(IV)	41400	ethyl 4-cyano-1-propyl-1H-pyrazol-3-yliminoformate		C₁₀H₁₄N₄O	详情	详情
(V)	41401	ethyl 4-cyano-2-propyl-1H-2lambda(5)-pyrazol-3-yliminoformate		C₁₀H₁₆N₄O	详情	详情
(VI)	41402	2-furohydrazide	3326-71-4	C₅H₆N₂O₂	详情	详情
(VII)	41403	2-(2-furyl)-8-propyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine		C₁₃H₁₂N₆O	详情	详情
(VIII)	41404	4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]-1-propyl-1H-pyrazol-3-amine; 4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]-1-propyl-1H-pyrazol-3-ylamine		C₁₂H₁₄N₆O	详情	详情
(IX)	41405	2-(2-furyl)-8-propyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ylamine; 2-(2-furyl)-8-propyl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine		C₁₃H₁₃N₇O	详情	详情
(X)	41406	4-methoxyphenyl isocyanate; 1-isocyanato-4-methoxybenzene	5416-93-3	C₈H₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The condensation between 3-(4-methoxyphenyl)propyl hydrazine (I) and (ethoxymethylene)malononitrile (II) afforded the pyrazole (III), which was transformed to the corresponding imidate (IV) by refluxing in triethyl orthoformate. Reaction of imidate (IV) with 2-furoic acid hydrazide (V) provided the pyrazolopyrimidine intermediate (VI), which was thermally cyclized in diphenyl ether to the tricyclic derivative (VII). Hydrolysis of (VII) with HCl induced the pyrimidine ring opening to furnish (VIII). This was finally converted into the title compound by treatment with cyanamide in N-methylpyrrolidone.

参考文献中间体

合成目标

【1】 Moresco, R.M.; Simonelli, P.; Todde, S.; et al.; Design, radiosynthesis, and biodistribution of a new potent and selective ligand for in vivo imaging of the adenosine A2A receptor system using positron emission tomography. J Med Chem 2000, 43, 23, 4359.

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)	47277	1-[3-(4-methoxyphenyl)propyl]hydrazine; 4-(3-hydrazinopropyl)phenyl methyl ether		C₁₀H₁₆N₂O	详情	详情
(II)	13017	Ethoxymethylenemalononitrile; 2-(Ethoxymethylene)malononitrile	123-06-8	C₆H₆N₂O	详情	详情
(III)	47278	5-amino-1-[3-(4-methoxyphenyl)propyl]-1H-pyrazole-4-carbonitrile		C₁₄H₁₆N₄O	详情	详情
(IV)	47279	ethyl 4-cyano-1-[3-(4-methoxyphenyl)propyl]-1H-pyrazol-5-yliminoformate		C₁₇H₂₀N₄O₂	详情	详情
(V)	41402	2-furohydrazide	3326-71-4	C₅H₆N₂O₂	详情	详情
(VI)	47280	N-[4-imino-1-[3-(4-methoxyphenyl)propyl]-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-yl]-2-furamide		C₂₀H₂₀N₆O₃	详情	详情
(VII)	47281	2-(2-furyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine; 4-[3-[2-(2-furyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl]propyl]phenyl methyl ether		C₂₀H₁₈N₆O₂	详情	详情
(VIII)	47282	4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]-1-[3-(4-methoxyphenyl)propyl]-1H-pyrazol-5-amine; 4-[3-(2-furyl)-1H-1,2,4-triazol-5-yl]-1-[3-(4-methoxyphenyl)propyl]-1H-pyrazol-5-ylamine		C₁₉H₂₀N₆O₂	详情	详情

Extended Information