Trifluoroacetic acid → N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-yl)acetamide

HRID 1621694Notes

Reaction equation

HRID 1621694 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:33][C:34]4[CH:35]=[CH:36][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[N:38][CH:39]=4)=[N:18][CH:19]=[C:20]([CH2:22][N:23]4[CH2:28][CH2:27][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:25][CH2:24]4)[CH:21]=3)[N:10]=2)=CC=1.FC(F)(F)S(O)(=O)=O.C(O)(C(F)(F)F)=O.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[C:17]([NH:33][C:34]3[CH:35]=[CH:36][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[N:38][CH:39]=3)=[N:18][CH:19]=[C:20]([CH2:22][N:23]3[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:27][CH2:28]3)[CH:21]=2)[N:10]=1

Participants

6

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 66611488N-(5-(3-(4-(bis(4-Methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-yl)acetamide

Product 1

HCID 59548421N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-yl)acetamideYield 66%

Procedure

N-(5-(3-(4-(bis(4-Methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-yl)acetamide (0.0806 g, 0.107 mmol) and trifluoromethanesulfonic acid (0.02 mL, 0.2 mmol) were dissolved into TFA (2 mL). The pale yellow solution was stirred at rt for 30 min. Then the mixture was stirred at 65° C. for overnight. After cooling to rt, solid sodium carbonate was added followed by aq sodium bicarbonate. The resulting greenish solid was collected and the crude product was purified by preparative HPLC using Phenomenex, Gemni 5 micron C18 100×30 mm column (1%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min). The fractions containing product were collected and concentrated to dryness in vacuo. The yellow residue was taken up in aq. sat'd sodium bicarbonate and sonicated. The resulting yellow solid was collected and washed with water and dried in a vacuum oven overnight to give N-(5-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)pyridin-2-yl)acetamide (0.0361 g, 66% yield). 1H NMR (400 MHz, d6-DMSO) δ 11.90 (s, 1H); 10.35 (s, 1H); 8.74 (d, J=2.54 Hz, 1H); 8.71 (d, J=2.54 Hz, 1H); 8.21-8.28 (m, 2H); 8.02 (d, J=9.00 Hz, 1H); 7.89 (br. s., 1H); 7.74 (br. s., 1H); 3.49 (s, 2H); 3.10 (d, J=4.50 Hz, 4H); 2.86 (s, 3H); 2.44 (s, 3H); 2.07 (s, 3H). 4 protons on the piperazine were buried under the water peak and could not be integrated. m/z (ESI, +ve ion) 513.0 (M+H)+.

Workup

  1. stirringThen the mixture was stirred at 65° C. for overnight
  2. temperatureAfter cooling to rt
  3. customThe resulting greenish solid was collected
  4. customthe crude product was purified by preparative HPLC
  5. customC18 100×30 mm column (1%-90% CH3CN w/0.1% TFA/H2O w/0.1% TFA in 10 min)
  6. additionThe fractions containing product
  7. customwere collected
  8. concentrationconcentrated to dryness in vacuo
  9. customsonicated
  10. customThe resulting yellow solid was collected
  11. washwashed with water
  12. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-0baad3e662d04c34b04ff5f5c954dddb
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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