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

HRID 1621676Notes

Reaction equation

HRID 1621676 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]=[CH:35][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:34]=[CH:35][CH:36]=[CH:37][CH:38]=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 666119881-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-phenylurea

Product 1

HCID 595482161-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-phenylureaYield 47%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
50 °C

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-phenylurea (0.0707 g, 0.108 mmol) and trifluoromethanesulfonic acid (TCI) (0.02 mL, 0.225 mmol) in 1 mL of TFA was stirred at rt for 3 h then heated to 50° C. and stirred for 3 h. Then the mixture was heated at 75° C. 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-phenylurea (0.0210 g, 47% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.87 (s, 1H); 10.28 (br. s., 1H); 9.30 (s, 1H); 8.71-8.84 (m, 2H); 8.34 (dd, J=4.60, 1.86 Hz, 1H); 8.22 (dd, J=9.00, 2.74 Hz, 1H); 7.87 (br. s., 1H); 7.74 (br. s., 1H); 7.47-7.58 (m, 3H); 7.31 (t, J=7.92 Hz, 2H); 7.01 (t, J=7.43 Hz, 1H); 6.92 (dd, J=7.83, 4.69 Hz, 1H); 2.44 (s, 3H). m/z (ESI, +ve ion) 414.0 (M+H)+.

Workup

  1. temperatureThen the mixture was heated at 75° C. overnight
  2. customto quench
  3. customthe reaction
  4. filtrationthe resulting precipitate was collected by filtration
  5. customThe crude product was purified by preparative HPLC
  6. customC18 150×30 mm column (10%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  7. concentrationThe resulting fraction was concentrated to dryness in vacuo
  8. additionSaturated sodium bicarbonate was added to the residue
  9. filtrationthe resulting yellow precipitate was collected by filtration
  10. washwashed with water
  11. customdried in a vacuum oven

Sources & evidence

ORD record
ord-8d101f21646a4514aa12a1c1abed6c1a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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