isonicotinic acid -Drug Synthesis Database

【结构式】

【分子编号】25028

【品名】isonicotinic acid

【CA登记号】55-22-1

【分子式】C₆H₅NO₂

【分子量】123.11124

【元素组成】C 58.54% H 4.09% N 11.38% O 25.99%

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：(III)

Compound can be prepared in several different ways: 1) By treatment of pyridine-4-sulfonic acid (I) with NH4OH and ZnCl2 in an autoclave at 160 C. 2) By reduction of 4-nitropyridine (II) with SO2 in hot water or diluted H2SO4. 3) By treatment of pyridine-4-carboxylic acid (III) with NH3 at high temperature using CuO as catalyst. 4) By treatment of 4-chloropyridine (IV) or 3-chloropyridine (V) with KNH2 in liquid NH3. 5) By treatment of 4-iodopyridine (VI) or 3-iodopyridine (VII) with KNH2 in liquid NH3.

参考文献中间体

合成目标

【1】 Pieterse, M.J.; Den Hertog, H.J.; Rearrangements during aminations of halopyridines, presumably involving a pyridine intermediate. Recl Trav Chim Pays-Bas 1961, 80, 1376-86.
【2】 Suzuki, Y.; Reactions of 4-pyridine- and 4-quinolinesulfonic acids with amines. Yakugaku Zasshi 1961, 81, 1146-50.
【3】 Hayashi, E.; Yamanaka, H.; JP 6115616 .
【4】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Paton, D.M.; 4-Aminopyridine. Drugs Fut 1980, 5, 5, 221.
【5】 Rauch, F.C.; Arzoumanidis, G.G.; DE 2258227 .
【6】 Rauch, F.C.; Arzoumanidis, G.G.; US 3812137 .
【7】 Koenig, C.; et al.; DE 1270563 .

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)	39036	4-pyridinesulfonic acid		C₅H₅NO₃S	详情	详情
(II)	39037	4-nitropyridine		C₅H₄N₂O₂	详情	详情
(III)	25028	isonicotinic acid	55-22-1	C₆H₅NO₂	详情	详情
(IV)	32889	4-chloropyridine	7379-35-3	C₅H₄ClN	详情	详情
(V)	39038	3-chloropyridine	626-60-8	C₅H₄ClN	详情	详情
(VI)	39039	4-iodopyridine		C₅H₄IN	详情	详情
(VII)	29108	3-iodopyridine		C₅H₄IN	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The condensation of 5-methylindoline (I) with benzonitrile (II) by means of BCl3 and AlCl3 in dichloroethane gives the 7-benzoyl-5-methylindoline (III), which is cyclized with glycine methyl ester (IV) in pyridine yielding the tricyclic pyrrolobenzodiazepinone (V). The reaction of (V) with isoamyl nitrite and potassium tert-butoxide in THF affords the oxime (VI), which is reduced with H2 over Ru/C in methanol providing the racemic amine (VII). The optical resolution of (VII) with N-acetyl-L-phenylalanine gives the desired isomer (VIII), which is finally condensed with pyridine-4-carboxylic acid (IX) by means of O-[1-(ethoxycarbonyl)-1-cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate (TOTU) and DIEA in dichloromethane.

参考文献中间体

合成目标

【1】 Andrianjara, C.R.; Auclair, E.; Pascal, Y.; et al.; Synthesis and structure-activity relationships of 4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indoles: Novel PDE4 inhibitors. Bioorg Med Chem Lett 2000, 10, 1, 35.

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)	31641	5-methylindoline		C₉H₁₁N	详情	详情
(II)	25904	benzonitrile	100-47-0	C₇H₅N	详情	详情
(III)	31642	(5-methyl-2,3-dihydro-1H-indol-7-yl)(phenyl)methanone		C₁₆H₁₅NO	详情	详情
(IV)	17568	methyl 2-aminoacetate		C₃H₇NO₂	详情	详情
(V)	31643	9-methyl-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indol-4(3H)-one		C₁₈H₁₆N₂O	详情	详情
(VI)	31644	9-methyl-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indole-3,4-dione 3-oxime		C₁₈H₁₅N₃O₂	详情	详情
(VII)	31645	3-amino-9-methyl-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indol-4(3H)-one		C₁₈H₁₇N₃O	详情	详情
(VIII)	31646	(3R)-3-amino-9-methyl-1-phenyl-6,7-dihydro[1,4]diazepino[6,7,1-hi]indol-4(3H)-one		C₁₈H₁₇N₃O	详情	详情
(IX)	25028	isonicotinic acid	55-22-1	C₆H₅NO₂	详情	详情

Extended Information