Tetrabutylammonium Fluoride → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide

HRID 245931ノート

反応式

HRID 245931 の反応式
[O:1]1[CH2:5][CH2:4][N:3]=[C:2]1[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].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[O:1]1[CH2:5][CH2:4][N:3]=[C:2]1[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]

参加物

3

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 71288191HCID 71288191、化合物

生成物 1

HCID 712882002-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide収率 41.4%

反応条件

温度
60 °C

実験手順

In a small vial, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide (85 mg, 0.16 mmol) was dissolved in tetrabutylammonium fluoride (1.0 M in THF, 1.6 ml, 1.6 mmol). The yellow reaction mixture was stirred at 60° C. overnight then cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-5% MeOH) to afford 27 mg (40%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4,5-dihydro-oxazol-2-yl)-ethyl]-amide as an off-white solid. MS: (M+Na)+=430; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.93 (br. s., 1H), 9.14 (s, 1H), 8.69 (dd, J=9.1, 5.3 Hz, 1H), 8.57 (d, J=8.3 Hz, 1H), 8.49 (s, 1H), 7.69 (dd, J=9.8, 1.9 Hz, 1H), 7.14 (td, J=9.1, 2.3 Hz, 1H), 4.97 (quin, J=7.5 Hz, 1H), 4.27-4.39 (m, 2H), 4.16 (s, 3H), 3.79 (td, J=9.3, 4.3 Hz, 2H), 1.50 (d, J=7.2 Hz, 3H).

後処理

  1. temperaturethen cooled to room temperature
  2. customquenched with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialthen dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-5% MeOH)

出典と根拠

ORDレコード
ord-00837e1f424e4e399121f62a0082d76c
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…