Tetrabutylammonium Fluoride → 6-(4-Ethynyl-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 1010071ノート

反応式

HRID 1010071 の反応式
[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:17]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[C:26][Si](C)(C)C)=[CH:21][C:20]=3[CH3:31])=[C:16]([F:32])[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1.O>[CH:1]1([CH2:4][O:5][NH:6][C:7]([C:9]2[C:17]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[CH:26])=[CH:21][C:20]=3[CH3:31])=[C:16]([F:32])[C:12]3[N:13]=[CH:14][NH:15][C:11]=3[CH:10]=2)=[O:8])[CH2:3][CH2:2]1

参加物

5

反応物 2

HCID 2724141Tetrabutylammonium Fluoride2 回HCID 865905277-Fluoro-6-(2-methyl-4-trimethylsilanylethynyl-phenylamino)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxyamide

生成物 1

HCID 588906896-(4-Ethynyl-2-methyl-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide収率 66.1%

試薬・触媒・溶媒 2

HCID 962Water触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

7-Fluoro-6-(2-methyl-4-trimethylsilanylethynyl-phenylamino)-3H-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide 11bbb (0.020 g, 0.044 mmol) is dissolved in tetrahydrofuran (0.50 mL) and the reaction solution is cooled to 0° C. TBAF (50 uL, 0.050 mmol, 1 M solution in tetrahydrofuran) is added. The reaction mixture is warmed to room temperature and additional TBAF (25 uL, 0.025 mmol, 1 M solution in tetrahydrofuran) is added. The reaction mixture is stirred at 50° C. for 2 hours under N2. The reaction mixture is cooled to room temperature, a few drops of H2O are added and then it is concentrated under reduced pressure. The residue is purified by FCC (eluting with 20:1 methylene chloride:methanol) to yield 0.011 g (65%) of the pure desired product. MS APCI (−) m/z 377 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 10.56 (broad s, 1H), 8.12 (s, 1H), 7.99 (s, 1H), 7.28 (s, 1H), 7.11 (d, 1H), 6.42 (broad, 1H), 3.70 (br s, 2H), 2.96 (d, 1H), 2.37 (s, 3H), 0.85 (m, 1H), 0.50 (m, 2H), 0.22 (m, 2H).

後処理

  1. temperatureThe reaction mixture is warmed to room temperature
  2. temperatureThe reaction mixture is cooled to room temperature
  3. concentrationit is concentrated under reduced pressure
  4. customThe residue is purified by FCC (eluting with 20:1 methylene chloride:methanol)

出典と根拠

ORDレコード
ord-ebb07e53af204fc18aa6752d1ecb5f7c
出典データセット
uspto-grants-2011_07
特許番号
US07973170B2

反応ノート

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