Isonicotinohydrazide -Drug Synthesis Database

【结构式】

【分子编号】26079

【品名】Isonicotinohydrazide

【CA登记号】54-85-3

【分子式】C₆H₇N₃O

【分子量】137.1412

【元素组成】C 52.55% H 5.14% N 30.64% O 11.67%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(B)

A mixture of freshly distilled pyridine (A) and 1-chloro-2,4-dinitrobenzene (I) in dry acetone is allowed to reflux for 15 h. Removal of the solvent in vacuo affords a residue which is washed with ether, recrystallized in absolute ethanol and characterized as N-(2,4-dinitrophenyl)pyridinium chloride (II). To an ice-cooled solution of compound (II) in methanol, a suspension of isonicotinic acid hydrazide in methanol in five aliquots is added with stirring. Triethylamine is then added and the reaction is allowed to stand at room temperature overnight. The solid which precipitates is purified and characterized as compound (III). A suspension of compound (III) in dioxane:water (4:1 v/v) is heated under reflux for 12 h to afford a clear solution. Separation and purification of the products gives a yellowish crystalline solid of N-(4-pyridylcarbonylimino)pyridiniumylide (IV) and 2,4-dinitroaniline (V). A solution of compound (IV) in 95% ethanol is added dropwise to a solution of sodium borohydride in 95% ethanol pre-cooled to 0 C. After stirring for 4 h at 0 C, the reaction mixture is poured onto crushed ice and allowed to come to room temperature. Extraction with chloroform, drying and purification yields N-(4-pyridylcarbonylamino)-1,2,3,6-tetrahydropyridine.

参考文献中间体

合成目标

【1】 Knaus, E.E.; Redda, K.; J Heterocycl Chem 1976, 13, 1237.
【2】 Knaus, E.E.; Corleto, L.A.; Redda, K. (Canadian Patents & Development Ltd.); N-(Carbonylamino)-tetrahydropyridyl derivatives. CA 1094073; US 4338445 .
【3】 Knaus, E.E.; Brush, J.S.; Martí, A.; Redda, K.; PATP. Drugs Fut 1985, 10, 6, 465.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	26079	Isonicotinohydrazide	54-85-3	C₆H₇N₃O	详情	详情
(A)	29669	Pyridine	110-86-1	C₅H₅N	详情	详情
(I)	10378	1-Chloro-2,4-dinitrobenzene	97-00-7	C₆H₃ClN₂O₄	详情	详情
(II)	29670	1-(2,4-dinitrophenyl)pyridinium chloride		C₁₁H₈ClN₃O₄	详情	详情
(III)	29671	1-(2,4-dinitrophenyl)-2-(2-isonicotinoylhydrazino)pyridinium chloride		C₁₇H₁₃ClN₆O₅	详情	详情
(IV)	29672	N-(1-Pyridinio)-pyridine-4-carboxamidate		C₁₁H₉N₃O	详情	详情
(V)	29673	2,4-dinitroaniline; 2,4-dinitrophenylamine	97-02-9	C₆H₅N₃O₄	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 of 2,4-bis(1-pyrrolidinyl)-6-(1-piperazinyl)pyrimidine (I) with 3-(bromomethyl)-5-chlorobenzonitrile (II) gives the disubstituted piperazine derivative (III). The partial hydrolysis of the CN group of (III) with methanol/HCl yiedls the iminoether (IV), which is condensed with 4-pyridylcarbonylhydrazide (V) to afford the amidrazone (VI). Finally, this compound is cyclized by heating.

参考文献中间体

合成目标

【1】 van der Goot, H.; et al.; New antioxidants with strong free radical scavenging and xanthine oxidase inhibiting activity. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.243.

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)	26075	4-(1-piperazinyl)-2,6-di(1-pyrrolidinyl)pyrimidine		C₁₆H₂₆N₆	详情	详情
(II)	26076	3-(bromomethyl)-5-chlorobenzonitrile		C₈H₅BrClN	详情	详情
(III)	26077	3-chloro-5-([4-[2,6-di(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]methyl)benzonitrile		C₂₄H₃₀ClN₇	详情	详情
(IV)	26078	methyl 3-chloro-5-([4-[2,6-di(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]methyl)benzenecarboximidoate		C₂₅H₃₄ClN₇O	详情	详情
(V)	26079	Isonicotinohydrazide	54-85-3	C₆H₇N₃O	详情	详情
(VI)	26080	N'-[[3-chloro-5-([4-[2,6-di(1-pyrrolidinyl)-4-pyrimidinyl]-1-piperazinyl]methyl)phenyl](imino)methyl]isonicotinohydrazide		C₃₀H₃₇ClN₁₀O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Isoniazid (I) was treated with carbon disulfide and KOH to give potassium 4-pyridyl dithiocarbazinate (II). Cyclization of (II) in the presence of hydrazine produced the amino triazole (III). This was condensed with 5-bromoisatin (IV), yielding the imino adduct (V). Finally, Mannich reaction of (V) with piperidine (VI) and formaldehyde furnished the title compound.

参考文献中间体

合成目标

【1】 de Clercq, E.; Nath, G.; Pandeya, S.N.; Sriram, D.; Synthesis, antibacterial, antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin and its derivatives with triazole. Arzneim-Forsch Drug Res 2000, 50, 1, 55.

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)	26079	Isonicotinohydrazide	54-85-3	C₆H₇N₃O	详情	详情
(II)	43763	potassium 2-isonicotinoyl-1-hydrazinecarbodithioate		C₇H₆KN₃OS₂	详情	详情
(III)	43764	4-amino-5-(4-pyridinyl)-4H-1,2,4-triazole-3-thiol; 4-amino-5-(4-pyridinyl)-4H-1,2,4-triazol-3-ylhydrosulfide		C₇H₇N₅S	详情	详情
(IV)	42952	6,8,11-trihydroxy-7H-benzo[e]perimidin-7-one		C₁₅H₈N₂O₄	详情	详情
(V)	43765	5-bromo-3-[[3-(4-pyridinyl)-5-sulfanyl-4H-1,2,4-triazol-4-yl]imino]-1H-indol-2-one		C₁₅H₉BrN₆OS	详情	详情
(VI)	10158	Piperidine	110-89-4	C₅H₁₁N	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The known (methylmercapto)benzodiazepine (I) was condensed with isonicotinic hydrazide (II) in refluxing EtOH to give the intermediate hydrazinobenzodiazepine (III), which under the reaction conditions cyclized to the target triazolobenzodiazepine.

参考文献中间体

合成目标

【1】 Vega, S.; Madronero, R.; Synthesis of triazolo[4,3-d]-, tetrazolo[1,5-a]- and quinazolino[3,2-d] [1,4]benzodiazepines. J Heterocycl Chem 1978, 15, 7, 1127.

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)	50129	methyl 1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-5-yl sulfide; 1-methyl-5-(methylsulfanyl)-2,3-dihydro-1H-1,4-benzodiazepine		C₁₁H₁₄N₂S	详情	详情
(II)	26079	Isonicotinohydrazide	54-85-3	C₆H₇N₃O	详情	详情
(III)	50130	N'-(1-methyl-2,3-dihydro-1H-1,4-benzodiazepin-5-yl)isonicotinohydrazide		C₁₆H₁₇N₅O	详情	详情

Extended Information