Cesium carbonate → 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246267ノート

反応式

HRID 246267 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.Cl[CH2:31][C:32]([N:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1)=[O:33].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH2:31][C:32]([N:34]2[CH2:39][CH2:38][O:37][CH2:36][CH2:35]2)=[O:33])=[CH:4][CH:3]=1

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 74040Morpholine, 4-(chloroacetyl)-HCID 866779442-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

生成物 1

HCID 866779702-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde収率 68.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

A 5 ml microwave vial was charged with 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (300 mg, 0.73 mmol), 4-(2-chloroacetyl)morpholine (0.19 ml, 1.46 mmol), cesium carbonate (713 mg, 2.19 mmol) and DMF (3.3 ml). The vial was flushed with argon, sealed and heated in a microwave reactor at 100° C. for 2 h. The reaction mixture was quenched with water and extracted with diethyl ether (2×). The organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-70% EtOAc) to afford 268 mg (68%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a yellow powder.

後処理

  1. customThe vial was flushed with argon
  2. customsealed
  3. customThe reaction mixture was quenched with water
  4. extractionextracted with diethyl ether (2×)
  5. washThe organic layers were washed twice with water and once with brine
  6. dry with materialthen dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient 0-70% EtOAc)

出典と根拠

ORDレコード
ord-319a544b208e4f09a8b12a6a5f3f2492
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…