Phosphoric Acid → HCID 178458655, compound

HRID 1641389Notes

Reaction equation

HRID 1641389 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:23]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[NH:21][N:20]=2)=[N:4][C:5]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])=[N:6][CH:7]=1.[P:28](=[O:32])([OH:31])([OH:30])[OH:29]>CO>[P:28]([OH:32])([OH:31])([OH:30])=[O:29].[Cl:1][C:2]1[C:3]([NH:18][C:19]2[CH:23]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[NH:21][N:20]=2)=[N:4][C:5]([NH:8][C@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)[CH3:10])=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 1004Phosphoric AcidHCID 178458654HCID 178458654, compound

Product 1

HCID 178458655HCID 178458655, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

To a solution of 5-chloro-N2-[(1S)-1-(5-fluoropyridin-2-yl)ethyl]-N4-(5-isopropoxy-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (Example 6; 2.46 g, 6.28 mmol) in methanol (25 ml) was added a solution of phosphoric acid (85 wt % in water, 724 mg, 6.28 mmol) in methanol (10 ml). The resulting precipitate was heated to reflux and more methanol (25 ml) was added. The precipitate was allowed to stir at reflux for 1 hour before cooling down to room temperature. The solution was filtered and filter cake obtained was washed with methanol and transferred to a round bottomed-flask for recrystallization. A suspension of the salt in methanol (50 ml) was then heated to reflux. At reflux, methanol (125 ml) was added where dissolution occurred. The excess solvent was removed by distillation to a final volume of 75 ml. The flask was removed from the heat and the solution was allowed to cool to room temperature. The resulting precipitate was filtered, washed with methanol, and vacuum dried under N2 atmosphere (16 h) to afford 1.43 g (57% isolated yield) of the title compound. 1H NMR: 9.63 (s, 1H), 8.49 (s, 1H), 7.87-8.10 (m, 2H), 7.65 (t, J=8.67 Hz, 1H), 7.41 (dd, J=8.29, 4.52 Hz, 1H), 5.52 (s, 1H), 5.03 (br s, 1H), 4.65 (br s, 1H), 1.44 (d, J=6.78 Hz, 3H), 1.26 (d, J=6.03 Hz, 6H).

Workup

  1. temperatureThe resulting precipitate was heated
  2. temperatureto reflux
  3. temperatureat reflux for 1 hour
  4. filtrationThe solution was filtered
  5. filtrationfilter cake
  6. customobtained
  7. washwas washed with methanol
  8. customtransferred to a round bottomed-flask for recrystallization
  9. additionA suspension of the salt in methanol (50 ml)
  10. temperaturewas then heated to reflux
  11. temperatureAt reflux
  12. additionmethanol (125 ml) was added
  13. dissolutionwhere dissolution
  14. customThe excess solvent was removed by distillation to a final volume of 75 ml
  15. customThe flask was removed from the
  16. temperatureheat
  17. temperatureto cool to room temperature
  18. filtrationThe resulting precipitate was filtered
  19. washwashed with methanol, and vacuum
  20. customdried under N2 atmosphere (16 h)
  21. customto afford

Sources & evidence

ORD record
ord-7caa2b9bf6f64050bf337c321ff69971
Source dataset
uspto-grants-2012_02
Patent number
US08114989B2

Reaction notes

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