HCID 66611145, compound → HCID 59548406, compound

HRID 1812012Notes

Reaction equation

HRID 1812012 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([CH2:31][N:32]4[CH2:37][CH2:36][O:35][CH2:34][C:33]4=[O:38])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)[N:10]=2)=CC=1>OS(C(F)(F)F)(=O)=O.C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:17]=[C:18]([CH2:31][N:32]3[CH2:37][CH2:36][O:35][CH2:34][C:33]3=[O:38])[CH:19]=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[N:10]=1

Participants

4

Reactant 1

HCID 66611145HCID 66611145, compound

Product 1

HCID 59548406HCID 59548406, compoundYield 54.6%

Reagents, catalysts & solvents 2

HCID 62406Trifluoromethanesulfonic acidCatalystHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A few drops of triflic acid were added to a solution of 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-((6-methoxy-3-pyridinyl)amino)-3-pyridinyl)methyl)-3-morpholinone (0.115 g, 0.174 mmol) in 2 mL of TFA at RT. The mixture was heated to 80° C. for 1 h. The reaction was cooled and concentrated, but not to dryness. A few ice cubes were added and saturated NaHCO3 (aq.) was added until pH=7. The yellow solid was filtered washed with water, CH2Cl2, MeOH and Et2O and collected and dried under vacuum. The aqueous layer was extracted with 3/1 CHCl3/n-BuOH (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (4 g), eluting with a gradient of 0% to 10% MeOH in CH2Cl2. This material was combined with the yellow solid collected above to provide 4-((5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-((6-methoxy-3-pyridinyl)amino)-3-pyridinyl)methyl)-3-morpholinone (0.040 g, 0.095 mmol, 54.6% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.76 (s, 1H); 8.70 (dd, J=2.15, 0.39 Hz, 1H); 8.53 (dd, J=2.54, 0.39 Hz, 1H); 8.24 (dd, J=2.05, 0.49 Hz, 1H); 8.13-8.19 (m, 1H); 7.88 (br. s., 1H); 7.72 (br. s., 1H); 6.82 (d, J=8.80 Hz, 1H); 4.52 (s, 2H); 4.10 (s, 2H); 3.84 (s, 3H); 3.79-3.83 (m, 2H); 3.27-3.32 (m, 2H); 2.43 (s, 3H). m/z (ESI, +ve ion) 423.2 (M+H)+.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. additionA few ice cubes were added
  4. additionsaturated NaHCO3 (aq.) was added until pH=7
  5. filtrationThe yellow solid was filtered
  6. washwashed with water, CH2Cl2, MeOH and Et2O
  7. customcollected
  8. customdried under vacuum
  9. extractionThe aqueous layer was extracted with 3/1 CHCl3/n-BuOH (3×)
  10. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (4 g)
  14. washeluting with a gradient of 0% to 10% MeOH in CH2Cl2
  15. customcollected above

Sources & evidence

ORD record
ord-ae11f93ed5ad47de99acd34948e283d6
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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