Cesium carbonate → 5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246531Notes

Reaction equation

HRID 246531 reaction equation
C([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14](C3C4C(=CC=C(OC(F)F)C=4)NN=3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])(C)(C)C.BrCC1CC1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[N:15]1[CH:14]=[CH:13][N:12]=[C:11]2[NH:10][CH:9]=[C:8]([C:6]([NH2:5])=[O:7])[C:16]=12

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 81503BromomethylcyclopropaneHCID 712795662-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide

Product 1

HCID 866779755H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 92.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (117.1 mg, 221 μmol) and (bromomethyl)cyclopropane (386 mg, 250 μL, 2.86 mmol) in DMF (60 mL) under Ar, cesium carbonate (750 mg, 2.3 mmol) was added in a single portion. The reaction mixture was stirred at 70° C. After 18 h, the reaction was cooled to 25° C. and quenched with water (200 mL). The mixture was extracted with ethyl acetate (3×75 mL) and the organics were washed with brine (100 mL). The organics were dried over sodium sulfate and concentrated to give N-tert-butyl-2-(1-(cyclopropylmethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-5-(2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (120 mg, 205 μmol, 86%). MS (M)'=585; 1H NMR (DMSO-d6) δ: 9.14 (s, 1H), 8.59 (s, 1H), 8.20 (d, J=2.0 Hz, 1H), 7.93 (s, 1H), 7.87 (s, 1H), 7.41 (dd, J=2.0, 8.8 Hz, 1H), 7.21 (t, J=74.3 Hz, 1H), 5.86 (m, 1H), 5.07 (dd, J=1.5, 17.1 Hz, 1H), 4.98 (d, J=10.3 Hz, 1H), 4.64 (t, J=7.0 Hz, 2H), 3.58 (t, J=8.0 Hz, 2H), 2.70 (m, 2H), 1.51 (s, 9H), 0.86 (t, J=8.0 Hz, 2H), −0.08 (s, 9H).

Workup

  1. temperaturethe reaction was cooled to 25° C.
  2. customquenched with water (200 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×75 mL)
  4. washthe organics were washed with brine (100 mL)
  5. dry with materialThe organics were dried over sodium sulfate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-42eb11b932ca4a88a5b16e8675449678
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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