Trifluoroacetic acid → 4-(5-(Difluoromethoxy)-2-(6-methoxypyridin-3-ylamino)pyridin-3-YL)-6-methyl-1,3,5-triazin-2-amine

HRID 1812188Notes

Reaction equation

HRID 1812188 reaction equation
[F:1][CH:2]([F:45])[O:3][C:4]1[CH:5]=[C:6]([C:19]2[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([N:26](CC3C=CC(OC)=CC=3)CC3C=CC(OC)=CC=3)[N:20]=2)[C:7]([NH:10][C:11]2[CH:12]=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)=[N:8][CH:9]=1.FC(F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O>>[F:45][CH:2]([F:1])[O:3][C:4]1[CH:5]=[C:6]([C:19]2[N:24]=[C:23]([CH3:25])[N:22]=[C:21]([NH2:26])[N:20]=2)[C:7]([NH:10][C:11]2[CH:12]=[N:13][C:14]([O:17][CH3:18])=[CH:15][CH:16]=2)=[N:8][CH:9]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 62406Trifluoromethanesulfonic acidHCID 666120174-(5-(Difluoromethoxy)-2-(6-methoxypyridin-3-ylamino)pyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595483574-(5-(Difluoromethoxy)-2-(6-methoxypyridin-3-ylamino)pyridin-3-YL)-6-methyl-1,3,5-triazin-2-amineYield 74%

Procedure

A solution of 4-(5-(difluoromethoxy)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.022 g, 0.036 mmol) in trifluoroacetic acid (Aldrich) (0.531 mL, 7.15 mmol) and trifluoromethane sulfonic acid (TCI) (3.16 μL, 0.036 mmol) was heated at 80° C. for 20 min. The reaction mixture was concentrated and the residue was first diluted with sat. NaHCO3 (8 mL) then extracted with CHCl3 (3×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (12 g, 10% to 20% acetone in hexanes) to give the product as a yellow solid (0.010 g). m/z (ESI, +ve ion) 376.0 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 11.65 (s, 1H); 8.67 (br. s., 1H); 8.35 (br. s., 1H); 8.20 (br. s., 1H); 8.09 (d, J=9.94 Hz, 1H); 6.79 (d, J=8.92 Hz, 1H); 6.11-6.75 (m, 1H); 5.41 (br. s., 2H); 3.95 (s, 3H); 2.58 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionthe residue was first diluted with sat. NaHCO3 (8 mL)
  3. extractionthen extracted with CHCl3 (3×10 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (12 g, 10% to 20% acetone in hexanes)

Sources & evidence

ORD record
ord-7fedde9e43f44570a9357bd398d68ee0
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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