Methanol → HCID 59548431, compound

HRID 1621708Notes

Reaction equation

HRID 1621708 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[CH:17]=[C:18]([CH2:31][N:32]4[CH2:37][CH2:36][N:35]([S:38]([N:41]([CH3:43])[CH3:42])(=[O:40])=[O:39])[CH2:34][CH2:33]4)[CH:19]=[N:20][C:21]=3[NH:22][C:23]3[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)[N:10]=2)=CC=1.FC(F)(F)C(O)=O.FC(F)(F)S(O)(=O)=O.CO>C(Cl)Cl>[NH2:8][C:9]1[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]2[CH:17]=[C:18]([CH2:31][N:32]3[CH2:33][CH2:34][N:35]([S:38]([N:41]([CH3:43])[CH3:42])(=[O:40])=[O:39])[CH2:36][CH2:37]3)[CH:19]=[N:20][C:21]=2[NH:22][C:23]2[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=2)[N:10]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 62406Trifluoromethanesulfonic acidHCID 59548187HCID 59548187, compound

Product 1

HCID 59548431HCID 59548431, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-((5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)-N,N-dimethylpiperazine-1-sulfonamide (0.210 g, 0.278 mmol) in trifluoroacetic acid (5 mL, 67.3 mmol) and trifluoromethanesulfonic acid (0.2 mL, 0.278 mmol) was stirred at 80° C. for 2 h. The dark solution was cooled down to room temperature and concentrated to a slurry. The slurry was neutralized to pH 8 with aqueous NaHCO3. The precipitate was dissolved in DCM/MeOH and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g) eluting with a gradient of 5% to 10% 2 M NH3.MeOH in CH2Cl2 to give 4-((5-(4-amino-6-methyl-1,3,5-triazin-2-yl)-6-(6-methoxypyridin-3-ylamino)pyridin-3-yl)methyl)-N,N-dimethylpiperazine-1-sulfonamide (0.110 g, 0.214 mmol, 77% yield). 1H NMR (400 MHz, d6-DMSO) δ 11.75 (s, 1H); 8.70 (d, J=2.15 Hz, 1H); 8.55 (d, J=0.39 Hz, 1H); 8.19 (d, J=2.54 Hz, 2H); 8.17 (dd, J=8.90, 2.84 Hz, 1H); 7.86 (d, J=0.98 Hz, 1H); 7.71 (d, J=1.76 Hz, 1H); 6.82 (d, J=8.80 Hz, 1H); 3.84 (s, 3H); 3.47 (s, 2H); 3.31 (s, 2H); 3.16 (d, J=4.89 Hz, 3H); 2.75 (s, 6H); 2.47 (s, 2H); 2.44 (s, 3H). m/z (ESI, +ve ion) 515.2 (M+H)+.

Workup

  1. concentrationconcentrated to a slurry
  2. dissolutionThe precipitate was dissolved in DCM/MeOH
  3. customchromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  4. washeluting with a gradient of 5% to 10% 2 M NH3

Sources & evidence

ORD record
ord-b8d0aacfccfc42a8bf1993e62d380416
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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