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 246321Notes

Reaction equation

HRID 246321 reaction equation
[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]

Participants

4

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-4aa84a2ec21443f2b7c7cacf2e7e734f
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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