3-Methyl-1-pentyn-3-ol → 3,4-difluoro-2-[2-fluoro-4-(3-hydroxy-3-methyl-1-pentynyl)anilino]-N-(2-hydroxyethoxy)benzamide

HRID 1793020ノート

反応式

HRID 1793020 の反応式
[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20](I)=[CH:19][C:18]=2[F:24])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].[CH3:25][C:26]([OH:31])([CH2:29][CH3:30])[C:27]#[CH:28]>CCOCC.CO.[Cu]I>[F:1][C:2]1[C:3]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:28]#[C:27][C:26]([OH:31])([CH3:25])[CH2:29][CH3:30])=[CH:19][C:18]=2[F:24])=[C:4]([CH:12]=[CH:13][C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6]

参加物

5

反応物 2

HCID 64943-Methyl-1-pentyn-3-olHCID 98038913,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)benzamide

生成物 1

HCID 101270833,4-difluoro-2-[2-fluoro-4-(3-hydroxy-3-methyl-1-pentynyl)anilino]-N-(2-hydroxyethoxy)benzamide収率 77%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 21864698Diethyl ether methanol溶媒

実験手順

3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide which can be prepared according to the procedure in PCT Publication No. WO 00/41505, and 3-methyl-1-pentyn-3-ol were reacted in the presence of CuI and (PhP3)2PdCl2 by the general procedure of Example 1, Step A, and the mixture stirred at RT for 4 h. The reaction mixture was diluted with 50% Et2O/MeOH and filtered through Celite®. The filtrate was concentrated under reduced pressure and further purified by flash chromatography on silica (CH2Cl2-10% MeOH/CH2Cl2 gradient elution) to give 3,4-difluoro-2-[2-fluoro-4-(3-hydroxy-3-methyl-1-pentynyl)anilino]-N-(2-hydroxyethoxy)benzamide (77%) as a white solid; m.p. (CH2Cl2/Hexane) 127–131° C.

後処理

  1. filtrationfiltered through Celite®
  2. concentrationThe filtrate was concentrated under reduced pressure
  3. customfurther purified by flash chromatography on silica (CH2Cl2-10% MeOH/CH2Cl2 gradient elution)

出典と根拠

ORDレコード
ord-93773aa78aea4709b88b8a4e3c2a60c6
出典データセット
uspto-grants-2006_07
特許番号
US07078438B2

反応ノート

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