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【结 构 式】

【分子编号】60058

【品名】6-iodo-4-(trifluoromethyl)-1H-indole-2,3-dione

【CA登记号】

【 分 子 式 】C9H3F3INO2

【 分 子 量 】341.0280396

【元素组成】C 31.7% H 0.89% F 16.71% I 37.21% N 4.11% O 9.38%

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:(VII)

Iodination of 3-(trifluoromethyl)nitrobenzene (I) was accomplished by using N-iodosuccinimide in concentrated sulfuric acid to provide (II), which was then reduced to aniline (III) with SnCl2 in refluxing EtOH. Treatment of aniline (III) with sulfuryl chloride, followed by addition of ethyl (methylthio)acetate and Et3N gave rise to a mixture of regioisomeric 3-(methylthio)oxindoles (IV) and (V). Oxidation of this mixture with CuCl2/CuO generated the respective isatins (VI) and (VII) (1). After N-alkylation with 2-(diethylamino)ethyl chloride and NaH, the desired regioisomer (VIII) could be separated by column chromatography. Addition to (VIII) of the Grignard reagent (IX) provided the racemic 3-aryl-3-hydroxy oxindole (X). The enantiomers of (X) were separated using chiral, preparative HPLC, and the desired (S)-enantiomer (XI) was then converted to nitrile (XII) by iodide displacement with zinc cyanide in the presence of palladium catalyst. Finally, partial hydrolysis of nitrile (XII) with KOH in tert-butanol furnished the title amide

1 Tokunaga, T.; Hume, W.E.; Umezome, T.; Okazaki, K.; Yasuyuki, U.; Kumagai, K.; Hourai, S.; Nagamine, J.; Seki, H.; Taiji, M.; Noguchi, H.; Nagata, R.; Oxindole derivatives as orally active potent growth hormone secretagogues. J Med Chem 2001, 44, 26, 4641.
2 Okazaki, K.; Kumagai, K.; Tokunaga, T.; Ueki, Y.; Nagata, R.; Umezome, T.; Hume, W.E. (Sumitomo Pharmaceuticals Co., Ltd.); Oxindole derivs. as growth hormone releasers. EP 1105376; JP 2002523400; WO 0010975 .
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) 16194 2-chloro-N,N-diethyl-1-ethanamine; N-(2-chloroethyl)-N,N-diethylamine 100-35-6 C6H14ClN 详情 详情
(A) 48543 Ethyl methylthioacetate; (Methylthio)acetic acid ethyl ester; ethyl 2-(methylsulfanyl)acetate 4455-13-4 C5H10O2S 详情 详情
(I) 26346 1-nitro-3-(trifluoromethyl)benzene 98-46-4 C7H4F3NO2 详情 详情
(II) 60054 1-iodo-3-nitro-5-(trifluoromethyl)benzene C7H3F3INO2 详情 详情
(III) 60055 3-iodo-5-(trifluoromethyl)phenylamine; 3-iodo-5-(trifluoromethyl)aniline C7H5F3IN 详情 详情
(IV) 60057 4-iodo-3-(methylsulfanyl)-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one C10H7F3INOS 详情 详情
(V) 60056 6-iodo-3-(methylsulfanyl)-4-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one C10H7F3INOS 详情 详情
(VI) 60059 4-iodo-6-(trifluoromethyl)-1H-indole-2,3-dione C9H3F3INO2 详情 详情
(VII) 60058 6-iodo-4-(trifluoromethyl)-1H-indole-2,3-dione C9H3F3INO2 详情 详情
(VIII) 60060 1-[2-(diethylamino)ethyl]-6-iodo-4-(trifluoromethyl)-1H-indole-2,3-dione C15H16F3IN2O2 详情 详情
(IX) 60061 (2-chlorophenyl)(iodo)magnesium C6H4ClIMg 详情 详情
(X) 60062 3-(2-chlorophenyl)-1-[2-(diethylamino)ethyl]-3-hydroxy-6-iodo-4-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one C21H21ClF3IN2O2 详情 详情
(XI) 60063 (3S)-3-(2-chlorophenyl)-1-[2-(diethylamino)ethyl]-3-hydroxy-6-iodo-4-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one C21H21ClF3IN2O2 详情 详情
(XII) 60064 (3S)-3-(2-chlorophenyl)-1-[2-(diethylamino)ethyl]-3-hydroxy-2-oxo-4-(trifluoromethyl)-2,3-dihydro-1H-indole-6-carbonitrile C22H21ClF3N3O2 详情 详情
Extended Information