Tetrabutylammonium Fluoride → HCID 71285779、化合物

HRID 246236ノート

反応式

HRID 246236 の反応式
[C:1]([CH2:3][O:4][CH2:5][C@@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[N:13](COCC[Si](C)(C)C)[CH:12]=1)=[O:10])[CH3:7])#[N:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:1]([CH2:3][O:4][CH2:5][C@@H:6]([NH:8][C:9]([C:11]1[C:19]2[C:14](=[N:15][CH:16]=[C:17]([C:20]3[C:28]4[C:23](=[CH:24][C:25]([F:29])=[CH:26][CH:27]=4)[N:22]([CH3:30])[N:21]=3)[N:18]=2)[NH:13][CH:12]=1)=[O:10])[CH3:7])#[N:2]

参加物

4

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 712860532-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyanomethoxy-1-methyl-ethyl)-amide

生成物 1

HCID 71285779HCID 71285779、化合物収率 16.8%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

In a round-bottomed flask containing 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyanomethoxy-1-methyl-ethyl)-amide (55 mg, 0.102 mmol) dissolved in THF (1 ml) was added TBAF (1.0 M in THF, 1.0 ml, 1.0 mmol). The flask was backfilled with nitrogen then sealed and placed in an oil bath at 85° C. for 2 h. The reaction was cooled to room temperature, quenched with acetone (2 ml) and sat'd NaHCO3 (4 ml). The mixture was stirred for 1 h then diluted with water and extracted twice with EtOAc. The combined organics were washed with water and brine then dried over MgSO4, filtered and concentrated. The crude solid was purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane. The appropriate fractions were combined and concentrated. The solid was triturated with Et2O to afford 7 mg (16%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-cyanomethoxy-1-methyl-ethyl)-amide as a light brown solid. LC-MS (M+H)+=408; 1H NMR (300 MHz, DMSO-d6) δ: 12.95 (br. s., 1H), 9.17 (s, 1H), 8.47-8.62 (m, 2H), 8.26 (d, J=8.5 Hz, 1H), 7.76 (dd, J=9.8, 2.0 Hz, 1H), 7.25 (td, J=9.0, 2.3 Hz, 1H), 4.57 (s, 2H), 4.43-4.53 (m, 1H), 4.21 (s, 3H), 3.66-3.85 (m, 2H), 1.40 (d, J=6.8 Hz, 3H).

後処理

  1. customthen sealed
  2. customquenched with acetone (2 ml) and sat'd NaHCO3 (4 ml)
  3. additionthen diluted with water
  4. extractionextracted twice with EtOAc
  5. washThe combined organics were washed with water and brine
  6. dry with materialthen dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude solid was purified by flash chromatography (4 g silicycle) with 0% to 10% MeOH in dichloromethane
  10. concentrationconcentrated
  11. customThe solid was triturated with Et2O

出典と根拠

ORDレコード
ord-73e918d7a1eb48619613960caef0d451
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…