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

HRID 1621680Notes

Reaction equation

HRID 1621680 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][CH:33]([CH3:35])[CH3:34])=[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)(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][CH:33]([CH3:35])[CH3:34])=[O:31])=[N:27][CH:28]=3)=[N:18][CH:19]=[CH:20][CH:21]=2)[N:10]=1

Participants

4

Reactant 2

HCID 62406Trifluoromethanesulfonic acid2×HCID 666003931-(5-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-isopropylurea

Product 1

HCID 595482531-(5-(3-(4-Amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-isopropylureaYield 49%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent2×

Conditions

Temperature
70 °C

Procedure

A stirred 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-isopropylurea (0.104 g, 0.168 mmol) in TFA (2 mL) was treated with trifluoromethanesulfonic acid (TCI) (0.02 mL, 0.2 mmol) and the reaction mixture was stirred at 70° C. for 2 h, then 80° C. for 2 h. TFA (2 mL) and trifluoromethanesulfonic acid (0.05 mL) were added. The heating was resumed at 75° C. for another 2 h. The mixture was cooled to rt, and some of the TFA was removed in vacuo. Sat'd NaHCO3 was added slowly until effervescence was no longer observed. The aqueous phase was extracted with 25% iPrOH in CHCl3+1% NH4OH (3×10 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (25 g, eluent: iPrOH (w/10% NH4OH) in CHCl3 0%-10%) to give 1-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-ylamino)pyridin-2-yl)-3-isopropylurea (0.0312 g, 49% yield) as a yellow powder. 1H NMR (300 MHz, d6-DMSO) δ 11.77 (s, 1H); 8.92 (s, 1H); 8.77 (d, J=7.75 Hz, 1H); 8.65 (br. s., 1H); 8.31 (br. s., 1H); 8.10 (br. s., 1H); 7.85 (br. s., 2H); 7.71 (br. s., 1H); 7.38 (d, J=8.92 Hz, 1H); 6.80-6.99 (m, 1H); 3.77-3.91 (m, 1H); 2.43 (s, 3H); 1.15 (d, J=6.28 Hz, 6H). m/z (ESI, +ve ion) 380.1 (M+H)+.

Workup

  1. wait80° C. for 2 h
  2. waitThe heating was resumed at 75° C. for another 2 h
  3. temperatureThe mixture was cooled to rt
  4. customsome of the TFA was removed in vacuo
  5. additionSat'd NaHCO3 was added slowly until effervescence
  6. extractionThe aqueous phase was extracted with 25% iPrOH in CHCl3+1% NH4OH (3×10 mL)
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel chromatography (25 g, eluent: iPrOH (w/10% NH4OH) in CHCl3 0%-10%)

Sources & evidence

ORD record
ord-73747e4e4cf84c5d89eab67628a66593
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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