• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】12290

【品名】N-[(1S)-1-Phenylethyl]-N-[(3R)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]amine; (3R)-N-[(1S)-1-Phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-3-amine

【CA登记号】

【 分 子 式 】C20H22N2

【 分 子 量 】290.40816

【元素组成】C 82.72% H 7.64% N 9.65%

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:(III)

The synthesis of Bay u 3405 was carried out as follows: Reductive amination of 3-oxo-1,2,3,4-tetrahydrocarbazole (I) with S-phenethylamine (II) afforded a mixture of diastereomeric amines, of which the desired isomer (III) crystallized in high diastereomeric purity as the hydrogensulfate. Cleavage of the phenethyl group by transfer hydrogenolysis with amminium formate and palladium on charcoal yielded the enantiomerically pure (3R)-3-amino-1,2,3,4-tetrahydrocarbazole (IV). Sulfonylation of (IV) with 4-fluorobenzenesulfonyl chloride (V) to the sulfonamide (VI) followed by addition of acrylonitrile and subsequent hydrolysis gave Bay u 3405.

1 Raz, A.; Needleman, P.; Minkes, M.; Thromboxanes: Selective biosynthesis and distinct biological properties. Science 1976, 193, 163-5.
2 Svensson, J.; Hamberg, M.; Samuelsson, B.; Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 1975, 72, 8, 2994-8.
3 Gardiner, P.J.; Boberg, M.; Fiedler, V.B.; Perzborn, E.; Boshagen, H.; Buhner, K.; Muller, U.; Rosentreter, U.; Seuter, F.; Weber, H.; Norman, P.; Ritter, W.; Bay u 3405. Drugs Fut 1991, 16, 8, 701.
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) 12288 1,2,4,9-Tetrahydro-3H-carbazol-3-one C12H11NO 详情 详情
(II) 20042 (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine C8H11N 详情 详情
(III) 12290 N-[(1S)-1-Phenylethyl]-N-[(3R)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]amine; (3R)-N-[(1S)-1-Phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-3-amine C20H22N2 详情 详情
(IV) 12291 (3R)-2,3,4,9-Tetrahydro-1H-carbazol-3-ylamine; (3R)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine C12H14N2 详情 详情
(V) 12292 4-Fluorobenzenesulfonyl chloride 349-88-2 C6H4ClFO2S 详情 详情
(VI) 12293 4-Fluoro-N-[(3R)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]benzenesulfonamide C18H17FN2O2S 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

The synthesis of [14C]-labeled Bay-u-3405 by two closely related ways has been described: 1) [14C]-Labeled aniline (I) is diazotized and reduced with sodium sulfite, yielding the labeled hydrazine (II), which is condensed with the monoketal of cyclohexane-1,4-dione (III) under Fisher's indole synthesis (ZnCl2) to afford the tetrahydrocarbazole (IV). The hydrolysis of (IV) with HCl in THF/water yields 1,2,3,4-tetrahydrocarbazol-3-one (V), which is submitted to a reductive condensation with (S)-1-phenylethylamine (VI) by means of tetrabutylammonium borohydride, yielding preferentially the secondary amine (VII), which, after purification, is dealkylated with ammonium formate and Pd/C to afford 1,2,3,4-tetrahydrocarbazole-3(R)-amine (VIII). The acylation of (VIII) with 4-fluorophenylsulfonyl chloride (IX) gives the corresponding sulfonamide (X), which is condensed with acrylonitrile by means of NaH, yielding 3-[3(R)-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydrocarbazol-9-yl]pro pionitrile (XI). Finally, this compound is hydrolyzed in the usual way. 2) The condensation of the sulfonamide (X) with methyl acrylate by means of NaH as before gives 3-[3(R)-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydrocarbazol-9-yl]propionic acid methyl ester (XII), which is finally hydrolyzed in the usual way.

1 Pleiss, U.; Radtke, M.; Rosentreter, U.; Boberg, M.; Synthesis of (+)-(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9-[5,6,7,8,12,13-u-C-14]carbazolepropanoic acid, [C-14]BAY u 3405. J Label Compd Radiopharm 1994, 34, 12, 1207.
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) 12294 Aniline; Phenylamine 62-53-3 C6H7N 详情 详情
(I) 45117   C6H7N 详情 详情
(II) 11818 Phenyl hydrazine; 1-Phenylhydrazine 100-63-0 C6H8N2 详情 详情
(II) 45118   C6H8N2 详情 详情
(III) 11377 1,4-Dioxaspiro[4.5]decan-8-one 4746-97-8 C8H12O3 详情 详情
(IV) 12297 1,2,3,4-Tetrahydrospiro[9H-carbazole-3,2'-1,3-dioxolane] C14H15NO2 详情 详情
(IV) 45119   C14H15NO2 详情 详情
(V) 12288 1,2,4,9-Tetrahydro-3H-carbazol-3-one C12H11NO 详情 详情
(V) 45120   C12H11NO 详情 详情
(VI) 20042 (1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine C8H11N 详情 详情
(VII) 12290 N-[(1S)-1-Phenylethyl]-N-[(3R)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]amine; (3R)-N-[(1S)-1-Phenylethyl]-2,3,4,9-tetrahydro-1H-carbazol-3-amine C20H22N2 详情 详情
(VII) 45121   C20H22N2 详情 详情
(VIII) 12291 (3R)-2,3,4,9-Tetrahydro-1H-carbazol-3-ylamine; (3R)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine C12H14N2 详情 详情
(VIII) 45122   C12H14N2 详情 详情
(IX) 12292 4-Fluorobenzenesulfonyl chloride 349-88-2 C6H4ClFO2S 详情 详情
(X) 12293 4-Fluoro-N-[(3R)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]benzenesulfonamide C18H17FN2O2S 详情 详情
(X) 45123   C18H17FN2O2S 详情 详情
(XI) 12304 N-[(3R)-9-(2-cyanoethyl)-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-4-fluorobenzenesulfonamide C21H20FN3O2S 详情 详情
(XI) 45124   C21H20FN3O2S 详情 详情
(XII) 12305 methyl 3-((3R)-3-[[(4-fluorophenyl)sulfonyl]amino]-1,2,3,4-tetrahydro-9H-carbazol-9-yl)propanoate C22H23FN2O4S 详情 详情
(XII) 45125   C22H23FN2O4S 详情 详情
Extended Information