Trifluoromethanesulfonic acid → HCID 59548343, compound

HRID 1621982Notes

Reaction equation

HRID 1621982 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]([C:32]([CH3:41])([CH3:40])[C:33]([O:35]C(C)(C)C)=[O:34])[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=3)[N:10]=2)=CC=1.FC(F)(F)S(O)(=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]([C:32]([CH3:41])([CH3:40])[C:33]([OH:35])=[O:34])[CH:19]=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:30][CH3:31])=[C:27]([F:29])[CH:28]=2)[N:10]=1

Participants

4

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 68518770HCID 68518770, compound

Product 1

HCID 59548343HCID 59548343, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

Tert-butyl 2-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)-2-methylpropanoate (25 mg, 0.035 mmol) was dissolved in TFA (344 μL), trifluoromethanesulfonic acid (15.48 mg, 0.103 mmol) was added, and the resulding mixture was stirred at 80° C. for 4 h. The reaction mixture was subsequently concentrated in vacuo and the residue was taken up in 100 mL of EtOAc, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0% to 100% EtOAc/hexanes) gave impure product which was further purified by preparatory TLC (2 plates; silica gel). TLC plates were loaded with the impure material and eluted in 10% MeOH/DCM to give the title compound (70% yield) following extraction of the product-containing bands with methanol, filtration, and concentration in vacuo. 1H NMR (400 MHz, d4-MeOH) δ 9.00 (d, J=2.74 Hz, 1H) 8.58 (s, 1H) 8.39 (d, J=2.54 Hz, 1H) 8.16-8.24 (m, 2H) 4.01 (s, 3H) 2.52 (s, 3H) 1.59 (s, 6H). m/z (ESI, +ve) 414.0 (M+H)+. m/z (ESI, +ve ion) 414.0 (M+H)+.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated in vacuo
  2. additionadded to a separatory funnel
  3. custompartitioned with sodium bicarbonate (saturated, aqueous)
  4. washwashed 2 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  5. customseparated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customChromatographic purification of the residue (silica gel, 0% to 100% EtOAc/hexanes)
  10. customgave impure product which
  11. customwas further purified by preparatory TLC (2 plates; silica gel)
  12. washeluted in 10% MeOH/DCM

Sources & evidence

ORD record
ord-9d21bcf004b040a5b104b9bf37a78f46
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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