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【结 构 式】

【分子编号】53893

【品名】9-methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one

【CA登记号】n/a

【 分 子 式 】C14H13NO

【 分 子 量 】211.26336

【元素组成】C 79.59% H 6.2% N 6.63% O 7.57%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

Mannich alpha-methylenation of N-methyltetrahydrocarbazolone (I) with morpholine in refluxing acetic and acid formaldehyde provides methylenecarbazolone derivative (II), which is then subjected to Michael addition with 2-methylimidazole (III) by means of alumina in refluxing toluene. Finally, formation of the desired hydrochloride dihydrate salt is obtained by treatment with HCl.

1 Kim, M.Y.; et al.; An efficient process of ondansetron synthesis. Heterocycles 1997, 45, 10, 2041.
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) 53889 9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one 27387-31-1 C13H13NO 详情 详情
(II) 53893 9-methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one n/a C14H13NO 详情 详情
(III) 15670 2-Methylimidazole; 2-Methyl-1H-imidazole 693-98-1 C4H6N2 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VI)

Treatment of tetrahydrocarbazolone (I) with formaldehyde and dimethylamine in EtOH provides tertiary amine (II), which is then methylated with refluxing iodomethane to furnish methanaminium iodide (III). Condensation of (III) with 2-methylimidazole (IV) in DMF affords free base (V), which is converted into the desired product, the hydrochloride dihydrate, by treatment with HCl in isopropanol/water. Alternatively, free base (V) can be obtained by other related procedures: (a) treatment of methanaminium iodide (III) with sodium carbonate in water to furnish methylene derivative (VI) followed by condensation with 2-methylimidazole (IV) in refluxing water; (b) conversion of (VI) into chloromethyl derivative (VII) by treatment with ethereal HCl in CHCl3, followed by reaction of (VII) with 2-methylimidazole (IV) in DMF; (c) treatment of dimethylamino derivative (VIII) with 2-methylimidazole (IV) in refluxing water; or (d) methylation of carbazolone (IX) with dimethylsulfate and sodium hydride in DMF.

1 Tyers, M.B. (GlaxoSmithKline plc); Ketone derivs.. EP 0275668; JP 1988253083; US 4845115 .
2 Coates, I.H.; Bell, J.A.; Ewan, G.B.; Humber, D.C. (GlaxoSmithKline plc); 1,2,3,9-Tetrahydro-3-imidazol-1-ylmethyl-4H-carbazol-4-ones, compsn. containing them, and method of using them to treat neuronal 5HT function disturbances. AU 8652614; EP 0191562; JP 1986210083; US 4695578 .
3 Coates, I.H.; Bell, J.A.; Hunber, D.C.; Ewan, G.B. (GlaxoSmithKline plc); Imidazolylmethyl substd. carbazoles. AU 8538097; BE 0901576; CH 664152; ES 8609309; ES 8708224; ES 8801247; FR 2561244; GB 2153821; JP 1985214784 .
4 Kraus, W.; Weisert, A.; Spies, J. (GlaxoSmithKline plc); Pharmaceutical product. DE 3740351 .
5 Kraus, W.; Weisert, A.; Spies, J. (GlaxoSmithKline plc); Pharmaceutical product. DE 3906883 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II),(VIII) 53904 3-[(dimethylamino)methyl]-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one n/a C16H20N2O 详情 详情
(I) 53889 9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one 27387-31-1 C13H13NO 详情 详情
(III) 53905 N,N,N-trimethyl(9-methyl-4-oxo-2,3,4,9-tetrahydro-1H-carbazol-3-yl)methanaminium iodide n/a C17H23IN2O 详情 详情
(IV) 15670 2-Methylimidazole; 2-Methyl-1H-imidazole 693-98-1 C4H6N2 详情 详情
(V) 53903 9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,9-tetrahydro-4H-carbazol-4-one n/a C18H19N3O 详情 详情
(VI) 53893 9-methyl-3-methylene-1,2,3,9-tetrahydro-4H-carbazol-4-one n/a C14H13NO 详情 详情
(VII) 53906 3-(chloromethyl)-9-methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one n/a C14H14ClNO 详情 详情
(IX) 53907 3-[(2-methyl-1H-imidazol-1-yl)methyl]-1,2,3,9-tetrahydro-4H-carbazol-4-one n/a C17H17N3O 详情 详情
Extended Information