Acetic Acid → 7-Methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate

HRID 522712Notes

Reaction equation

HRID 522712 reaction equation
[F:1][C:2]([F:21])([F:20])[S:3]([O:6][C:7]1[C:18]([CH3:19])=[N:17][C:10]2[N:11]=[C:12](SC)[N:13]=[CH:14][C:9]=2[CH:8]=1)(=[O:5])=[O:4].C(O)(=O)C.[O-]Cl.[Na+].[CH3:29][NH2:30].C1COCC1>CN(C)C=O>[F:1][C:2]([F:21])([F:20])[S:3]([O:6][C:7]1[C:18]([CH3:19])=[N:17][C:10]2[N:11]=[C:12]([NH:30][CH3:29])[N:13]=[CH:14][C:9]=2[CH:8]=1)(=[O:5])=[O:4]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 23665760Sodium HypochloriteHCID 898092287-Methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate

Product 1

HCID 898095047-Methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonateYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
47.5 °C

Procedure

Heat a mixture 7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (28.6 g, 84 mmol), dimethylformamide (74 mL) and glacial acetic acid (9.61 mL, 169 mmol) to 45° C. and then add 6.15% aqueous NaOCl (bleach, 612 g, 506 mmol) dropwise over 2 h. Heat at 45-50° C. for 2 h, cool to RT, collect the solids by filtration and wash with water (300 mL). Add DCM (200 mL) to the solids, cool the suspension in an ice-water bath and treat with a solution of 2.0 M N-methylamine in THF (126 mL, 253 mmol). Allow the mixture to slowly warm to RT and stir for 2 h. Remove the solvent under reduced pressure, treat with methanol (MeOH) (50 mL) and stir at RT for 30 min. Collect the solid by filtration and wash with MeOH. Treat the solid with EtOAc (30 mL) and stir at RT for 30 min. Collect the solid by filtration and wash with EtOAc to obtain the title compound (19.82 g, 73% yield). MS (m/z): 323.0 (M+1).

Workup

  1. temperaturecool to RT
  2. customcollect the solids
  3. filtrationby filtration
  4. washwash with water (300 mL)
  5. temperatureAdd DCM (200 mL) to the solids, cool the suspension in an ice-water bath
  6. temperatureAllow the mixture to slowly warm to RT
  7. customRemove the solvent under reduced pressure
  8. additiontreat with methanol (MeOH) (50 mL)
  9. stirringstir at RT for 30 min
  10. customCollect the solid
  11. filtrationby filtration
  12. washwash with MeOH
  13. additionTreat the solid with EtOAc (30 mL)
  14. stirringstir at RT for 30 min
  15. customCollect the solid
  16. filtrationby filtration
  17. washwash with EtOAc

Sources & evidence

ORD record
ord-215d0ed4cddf4d1c9b2fb0a114ea6f02
Source dataset
uspto-grants-2016_05
Patent number
US09334267B2

Reaction notes

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