Ammonia → 6-Tert-butyl-2,7-naphthyridin-1-amine

HRID 921035Notes

Reaction equation

HRID 921035 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]([C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:7][C:8]=1[CH3:9])#[N:2].[CH3:14][N:15](C=O)C.C([O-])(=O)C.[NH4+].N>O.C(O)C>[NH2:2][C:1]1[C:3]2[C:8](=[CH:7][C:6]([C:10]([CH3:13])([CH3:12])[CH3:11])=[N:5][CH:4]=2)[CH:9]=[CH:14][N:15]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6228DimethylformamideHCID 517165Ammonium AcetateHCID 534188646-Tert-butyl-4-methylnicotinonitrile

Product 1

HCID 587173846-Tert-butyl-2,7-naphthyridin-1-amine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Procedure analogous to A. Zhang et al., J. Combi. Chem. 2007, 9, 6, 916: A mixture of 17.4 g (100 mmol) of 3-cyano-4-methyl-6-tert-butylpyridine [942938-45-6], 14.0 ml (105 mmol) of N,N-dimethylformamind dimethyl acetal [4637-24-5] and 150 ml of DMF is heated under reflux for 16 h. The DMF is then removed at 70° C. in vacuo. 46.3 g (600 mmol) of anhydrous ammonium acetate are added to the oily residue, the mixture is homogenised, heated to melt ing in an oil bath (temperature about 135° C.) and stirred for 3 h. After cooling, the melt is taken up in a mixture of 200 ml of water and 100 ml of ethanol, rendered alkaline (pH about 9) by addition of conc. ammonia solution and extracted three times with 300 ml of dichloromethane each time. The combined org. phases are washed twice with 300 ml of water each time and dried over sodium sulfat e. Aft er evaporation of the org. phase in vacuo, the residue remaining is subjected to sublimation (p about 1×10−2 mbar, T=150° C.). Yield: 13.7 g (68 mmol), 68%. Purity: >95% according to 1H-NMR.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 16 h
  3. customThe DMF is then removed at 70° C. in vacuo
  4. temperatureheated
  5. custom(temperature about 135° C.)
  6. stirringstirred for 3 h
  7. temperatureAfter cooling
  8. extractionextracted three times with 300 ml of dichloromethane each time
  9. washphases are washed twice with 300 ml of water each time
  10. dry with materialdried over sodium sulfat e
  11. customAft er evaporation of the org
  12. customremaining is subjected to sublimation (p about 1×10−2 mbar, T=150° C.)

Sources & evidence

ORD record
ord-655ed3315e6b43a7b8f5c8045ce8268b
Source dataset
uspto-grants-2016_03
Patent number
US09273080B2

Reaction notes

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