Ethylenediamine → N-tert-butyl-2-(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246567Notes

Reaction equation

HRID 246567 reaction equation
[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[C:25]4[C:20](=[N:21][CH:22]=[CH:23][CH:24]=4)[N:19]([CH3:26])[N:18]=3)=[CH:15][N:16]=[C:11]2[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N)CN.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C.ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[C:25]4[C:20](=[N:21][CH:22]=[CH:23][CH:24]=4)[N:19]([CH3:26])[N:18]=3)=[CH:15][N:16]=[C:11]2[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 3301EthylenediamineHCID 2724141Tetrabutylammonium FluorideHCID 71280190N-tert-butyl-2-(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Product 1

HCID 71279725N-tert-butyl-2-(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamideYield 9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of N-tert-butyl-2-(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (306 mg, 638 μmol) in DMF (15 mL) was added ethylenediamine (1.92 g, 2.15 mL, 31.9 mmol) followed by TBAF (1.91 mL, 1.91 mmol) and the mixture heated at 60° C. under nitrogen for 15 h. The mixture was cooled, diluted with dichloromethane, washed with water and brine, then dried (MgSO4), filtered and concentrated to obtain an oil. This was triturated with water to remove tetrabutylammonium hydroxide, filtered, and the residue purified by chromatography (silica, 5-10% methanol in dichloromethane) to obtain N-tert-butyl-2-(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (19.2 mg, 55.0 μmol, 9%) as a light yellow powder. MS (M+H)+=350; 1H NMR (DMSO-d6) δ: 9.12 (s, 1H), 8.84 (dd, J=8.2, 1.6 Hz, 1H), 8.70 (dd, J=4.5, 1.5 Hz, 1H), 8.42 (s, 1H), 7.93 (s, 1H), 7.39 (dd, J=8.0, 4.5 Hz, 1H), 4.22 (s, 3H).

Workup

  1. temperatureThe mixture was cooled
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto obtain an oil
  7. customThis was triturated with water
  8. customto remove tetrabutylammonium hydroxide
  9. filtrationfiltered
  10. customthe residue purified by chromatography (silica, 5-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-51574b93004d4c73a238e384d8f4bba3
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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