Trifluoromethanesulfonic acid → 1-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone

HRID 1812217Notes

Reaction equation

HRID 1812217 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](=[O:34])[CH3:33])[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.S(O)(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]([C:32](=[O:34])[CH3:33])[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 666002411-(5-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-YL)ethanone

Product 1

HCID 665998701-(5-(4-Amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanoneYield 70.2%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 1-(5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (Example 271; 332 mg, 0.54 mmol) in TFA (3 mL) was treated with TfOH (0.1 mL). The solution was heated at 80° C. in an oil bath for 4 h, allowed to cool to room temperature, and concentrated. The dark residue was treated with a few ice cubes followed by sat. NaHCO3 while rapidly stirring. The precipitated yellow solid was collected by filtration and rinsed with water (5 mL). The yellow solid was purified by flash chromatography eluting with 1-15% MeOH in DCM to give 1-(5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(5-fluoro-6-methoxypyridin-3-ylamino)pyridin-3-yl)ethanone (140 mg, 69%) as a bright yellow crystalline solid. m/z (ESI, +ve ion) 460 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.38 (br., 1H); 9.26 (d, J=2.2 Hz, 1H); 8.96 (d, J=2.2 Hz, 1H); 8.42 (s, 1H); 8.35 (dd, J=12.3, 1.6 Hz, 1H); 8.00 (s, 1H); 7.83 (s, 1H); 3.96 (s, 3H); 2.57 (s, 3H); 2.46 (s, 3H).

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated
  3. additionThe dark residue was treated with a few ice cubes
  4. filtrationThe precipitated yellow solid was collected by filtration
  5. washrinsed with water (5 mL)
  6. customThe yellow solid was purified by flash chromatography
  7. washeluting with 1-15% MeOH in DCM

Sources & evidence

ORD record
ord-37c5fe81bf0e4075a83bd6bb40921bd4
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

Loading…