(5-methyl-2,3-dihydro-1H-indol-7-yl)(phenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】31642

【品名】(5-methyl-2,3-dihydro-1H-indol-7-yl)(phenyl)methanone

【CA登记号】

【分子式】C₁₆H₁₅NO

【分子量】237.30124

【元素组成】C 80.98% H 6.37% N 5.9% O 6.74%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

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