Acetonitrile → HCID 46215991, compound

HRID 2367287Notes

Reaction equation

HRID 2367287 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])[N:3]=1.O.[NH2:23][NH2:24].C(#N)C>CCO>[NH2:13][C:12]1[C:11]2[C:10](=[CH:9][C:8]([C:6]3[N:7]=[C:2]([NH2:1])[N:3]=[C:4]([NH:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:5]=3)=[CH:15][CH:14]=2)[NH:24][N:23]=1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 24654Hydrazine hydrate (1:1)HCID 58504644HCID 58504644, compound

Product 1

HCID 46215991HCID 46215991, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
95 °C

Procedure

Into a 25 mL sealable tube under nitrogen were combined 4-{2-amino-6-[(1,1-dimethylethyl)amino]-4-pyrimidinyl}-2-fluorobenzonitrile (500 mg, 1.25 mmol) and hydrazine monohydrate (1.22 mL) in EtOH (8 mL). The vial was sealed, and the reaction mixture was stirred at 95° C. for 22 hours. The solution was concentrated, partitioned between EtOAc and water, and extracted with EtOAC (2×) and CH2Cl2. The organic layer was separated, washed with NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The resulting solid was dissolved in a mixture of CH3CN/water/CH3OH/DMSO and purified on a Gilson RPHPLC (CH3CN/H2O w/0.1% TFA). Fractions were evaporated, aqueous potassium carbonate was added to the residue and the solution was stirred at room temperature for 2 hrs. The aqueous mixture was extracted with EtOAc (×2) and DCM (×2). The organic layer was separated, washed with brine, dried (MgSO4), filtered, concentrated and azeotroped with CH3CN to give a brown solid. Minimum amount of acetonitrile was added to the solids, and the resulting mixture was sonicated. A white precipitate crashed out which was filtered and washed with hexanes and Et2O to afford the title compound (102 mg) as a white solid. LC-MS (ES) m/z=298 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.42 (s, 9H), 5.36 (s, 2H), 5.90 (s, 2H), 6.31 (s, 1H), 6.53 (s, 1H), 7.36 (dd, J=8.6, 1.3 Hz, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.80 (s, 1H), 11.50 (s, 1H).

Workup

  1. customInto a 25 mL sealable tube under nitrogen were combined
  2. customThe vial was sealed
  3. concentrationThe solution was concentrated
  4. custompartitioned between EtOAc and water
  5. extractionextracted with EtOAC (2×) and CH2Cl2
  6. customThe organic layer was separated
  7. washwashed with NaHCO3 and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. dissolutionThe resulting solid was dissolved in a mixture of CH3CN/water/CH3OH/DMSO
  12. custompurified on a Gilson RPHPLC (CH3CN/H2O w/0.1% TFA)
  13. customFractions were evaporated
  14. additionaqueous potassium carbonate was added to the residue
  15. stirringthe solution was stirred at room temperature for 2 hrs
  16. extractionThe aqueous mixture was extracted with EtOAc (×2) and DCM (×2)
  17. customThe organic layer was separated
  18. washwashed with brine
  19. dry with materialdried (MgSO4)
  20. filtrationfiltered
  21. concentrationconcentrated
  22. customazeotroped with CH3CN
  23. customto give a brown solid
  24. customthe resulting mixture was sonicated
  25. filtrationwas filtered
  26. washwashed with hexanes and Et2O

Sources & evidence

ORD record
ord-70aa3496006f4becbfe769323e7a3928
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…