Trifluoromethanesulfonic acid → 1-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)urea

HRID 1621678Notes

Reaction equation

HRID 1621678 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[C:17]([NH:22][C:23]4[CH:24]=[CH:25][C:26]([NH:29][C:30]([NH:32][C:33]5[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=5)=[O:31])=[N:27][CH:28]=4)=[N:18][CH:19]=[CH:20][CH:21]=3)[N:10]=2)=CC=1.FC(F)(F)S(O)(=O)=O.C(=O)(O)[O-].[Na+]>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[C:17]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([NH:29][C:30]([NH:32][C:33]4[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=4)=[O:31])=[N:27][CH:28]=3)=[N:18][CH:19]=[CH:20][CH:21]=2)[N:10]=1

Participants

5

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 666117991-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)urea

Product 1

HCID 595482001-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)ureaYield 58%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 1-(5-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)urea (0.0824 g, 0.123 mmol) and trifluoromethanesulfonic acid (TCI) (0.02 mL, 0.225 mmol) in TFA (1 mL) was stirred at rt for 3 h, 50° C. for 3 h, then 75° C. for overnight. Saturated sodium bicarbonate was added slowly to quench the reaction and the resulting precipitate was collected by filtration. The crude product was purified by preparative HPLC using Phenomenex, Gemni NX 5 micron C18 150×30 mm column (10%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The resulting fraction was concentrated to dryness in vacuo. Saturated sodium bicarbonate was added to the residue and the resulting yellow precipitate was collected by filtration, washed with water, and dried in a vacuum oven to give 1-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-(3-fluorophenyl)urea (0.0305 g, 58% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.89 (s, 1H); 10.49 (br. s., 1H); 9.38 (s, 1H); 8.71-8.83 (m, 2H); 8.29-8.39 (m, 1H); 8.23 (dd, J=9.00, 2.35 Hz, 1H); 7.87 (br. s., 1H); 7.74 (br. s., 1H); 7.47-7.65 (m, 2H); 7.34 (q, J=7.89 Hz, 1H); 7.20 (d, J=8.02 Hz, 1H); 6.92 (dd, J=7.63, 4.69 Hz, 1H); 6.76-6.87 (m, 1H); 2.44 (s, 3H). m/z (ESI, +ve ion) 432.0 (M+H)+.

Workup

  1. customto quench
  2. customthe reaction
  3. filtrationthe resulting precipitate was collected by filtration
  4. customThe crude product was purified by preparative HPLC
  5. customC18 150×30 mm column (10%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  6. concentrationThe resulting fraction was concentrated to dryness in vacuo
  7. additionSaturated sodium bicarbonate was added to the residue
  8. filtrationthe resulting yellow precipitate was collected by filtration
  9. washwashed with water
  10. customdried in a vacuum oven

Sources & evidence

ORD record
ord-68b5826f616d41ee8cec85fa09d8f8a3
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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