Triacetoxyperiodinane → 2-(5-formyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

HRID 246321ノート

反応式

HRID 246321 の反応式
[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][OH:26])[CH:23]=4)[N:18]([CH3:27])[N:17]=3)[N:14]=2)[N:9]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[CH:8]=1)=[O:6])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl>[CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([C:16]3[C:24]4[C:19](=[CH:20][CH:21]=[C:22]([CH:25]=[O:26])[CH:23]=4)[N:18]([CH3:27])[N:17]=3)[N:14]=2)[N:9]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:33])[CH3:35])[CH:8]=1)=[O:6])([CH3:3])[CH3:2]

参加物

4

反応物 2

HCID 159087TriacetoxyperiodinaneHCID 712804422-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

生成物 1

HCID 866779732-(5-formyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide収率 71%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

In a round-bottomed flask, 2-(5-hydroxymethyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (crude from Step 2, 476 mg, 0.625 mmol) was dissolved in dichloromethane (3.2 ml) and Dess-Martin periodinane (292 mg, 0.688 mmol) was added. The reaction mixture was stirred at room temperature for 1.5 h then quenched with 10 ml of a 1:1 mixture of 10% aqueous Na2S2O3 and saturated aqueous NaHCO3 and extracted with dichloromethane. The organic layer was washed with saturated aqueous NaHCO3 then the aqueous layers were back-extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/Hexanes (gradient: 0-60% EtOAc) to afford 218 mg (71%) of 2-(5-formyl-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a light yellow solid. 1H NMR (CDCl3, 400 MHz): δ (ppm) 9.25 (s, 1H), 8.97 (dd, J=1.4, 0.9 Hz, 1H), 8.41 (s, 1H), 8.11 (d, J=8.6 Hz, 1H), 8.07 (dd, J=8.8, 1.5 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 5.75 (s, 2H), 4.42-4.53 (m, 1H), 4.26 (s, 3H), 3.56-3.64 (m, 2H), 1.41 (d, J=6.6 Hz, 6H), 0.92-1.00 (m, 2H), −0.03 (s, 9H).

後処理

  1. customthen quenched with 10 ml of a 1:1 mixture of 10% aqueous Na2S2O3 and saturated aqueous NaHCO3
  2. extractionextracted with dichloromethane
  3. washThe organic layer was washed with saturated aqueous NaHCO3
  4. extractionthe aqueous layers were back-extracted with dichloromethane
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was absorbed on silica gel
  9. customchromatographed with EtOAc/Hexanes (gradient: 0-60% EtOAc)

出典と根拠

ORDレコード
ord-4aa84a2ec21443f2b7c7cacf2e7e734f
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…