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

HRID 1812201Notes

Reaction equation

HRID 1812201 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:39]=[CH:38][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[CH:36][CH:35]=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)C(O)=O.FC(F)(F)S(O)(=O)=O.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:39]=[CH:38][C:37]([NH:40][C:41](=[O:43])[CH3:42])=[CH:36][CH:35]=3)=[N:18][CH:19]=[C:20]([CH2:22][N:23]3[CH2:24][CH2:25][N:26]([S:29]([CH3:32])(=[O:30])=[O:31])[CH2:27][CH2:28]3)[CH:21]=2)[N:10]=1

Participants

5

Reactant 4

HCID 6422Trifluoroacetic acidHCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 66612119N-(4-(3-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-5-((4-(methylsulfonyl)piperazin-1-YL)methyl)pyridin-2-ylamino)phenyl)acetamide

Product 1

HCID 59548352N-(4-(3-(4-Amino-6-methyl-1,3,5-triazin-2-YL)-5-((4-(methylsulfonyl)piperazin-1-YL)methyl)pyridin-2-ylamino)phenyl)acetamideYield 73.6%

Procedure

A solution of N-(4-(3-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-ylamino)phenyl)acetamide (0.140 g, 0.186 mmol) in trifluoroacetic acid (Aldrich) (1.383 mL, 18.62 mmol) and trifluoromethane sulfonic acid (TCI) (0.494 mL, 5.59 mmol) was stirred at rt in a sealed tube for 1 h. The reaction mixture was first neutralized with sat. NaHCO3 then extracted with CHCl3 (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (120 g, 4% MeOH in DCM) to give the product as a yellow solid (0.070 g). m/z (ESI, +ve ion) 512.0 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 11.85 (s, 1H); 8.72 (s, 1H); 8.28 (d, J=0.73 Hz, 1H); 7.68 (s, 2H); 7.48 (d, J=8.48 Hz, 2H); 7.12 (br. s., 1H); 5.43 (br. s., 2H); 3.53 (s, 2H); 3.26 (br. s., 4H); 2.78 (s, 3H); 2.59 (s, 7H); 2.19 (s, 3H).

Workup

  1. extractionthen extracted with CHCl3 (2×10 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. concentrationconcentrated
  4. customThe crude product was purified by column chromatography (120 g, 4% MeOH in DCM)

Sources & evidence

ORD record
ord-93b150bec55147609cf4db4be42c11da
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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