Trifluoroacetic acid → 4-(2-(6-Methoxypyridin-3-ylamino)-5-((1-(methylsulfonyl)piperidin-4-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621604Notes

Reaction equation

HRID 1621604 reaction equation
COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[N:14]=[C:13]([C:15]3[C:16]([NH:32][C:33]4[CH:34]=[N:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=4)=[N:17][CH:18]=[C:19]([CH2:21][CH:22]4[CH2:27][CH2:26][N:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:24][CH2:23]4)[CH:20]=3)[N:12]=[C:11]([CH3:41])[N:10]=2)=CC=1.C(O)(C(F)(F)F)=O>CS(O)(=O)=O>[CH3:40][O:39][C:36]1[N:35]=[CH:34][C:33]([NH:32][C:16]2[C:15]([C:13]3[N:12]=[C:11]([CH3:41])[N:10]=[C:9]([NH2:8])[N:14]=3)=[CH:20][C:19]([CH2:21][CH:22]3[CH2:27][CH2:26][N:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:24][CH2:23]3)=[CH:18][N:17]=2)=[CH:38][CH:37]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 60155985N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-((1-(methylsulfonyl)piperidin-4-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595484244-(2-(6-Methoxypyridin-3-ylamino)-5-((1-(methylsulfonyl)piperidin-4-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 68.7%

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidCatalyst

Conditions

Temperature
80 °C

Procedure

A suspension of N,N-bis(4-methoxybenzyl)-4-(2-(6-methoxypyridin-3-ylamino)-5-((1-(methylsulfonyl)piperidin-4-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.1923 g, 0.265 mmol) in TFA (1.022 mL, 13.26 mmol) was treated with a couple of drops of methanesulfonic acid (0.017 mL, 0.265 mmol) and the yellow solution was heated at 80° C. overnight. The volatile material was removed and the residue was carefully diluted with 5% 2 M NH3 in MeOH/DCM. The solution was concentrated with SiO2 and chromatographed through a Redi-Sep pre-packed silica gel column (pure DCM→10% MeOH in DCM w/NH3). Following concentration of the eluent, the resulting yellow solid was washed with IPA to give 4-(2-(6-methoxypyridin-3-ylamino)-5-((1-(methylsulfonyl)piperidin-4-yl)methyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (88 mg, 0.182 mmol, 68.5% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 11.66 (s, 1H); 8.60 (d, J=2.54 Hz, 1H); 8.54 (d, J=2.54 Hz, 1H); 8.17 (dd, J=8.90, 2.64 Hz, 1H); 8.14 (d, J=2.15 Hz, 1H); 7.84 (br. s., 1H); 7.71 (br. s., 1H); 6.81 (d, J=8.80 Hz, 1H); 3.84 (s, 3H); 3.45-3.62 (m, 2H); 2.82 (s, 3H); 2.61-2.72 (m, 2H); 2.43 (s, 3H); 1.67-1.68 (m, 2H); 1.46-1.64 (m, 1H); 1.15-1.32 (m, 2H). m/z (ESI, +ve ion) 485.2 (M+H)+.

Workup

  1. customThe volatile material was removed
  2. additionthe residue was carefully diluted with 5% 2 M NH3 in MeOH/DCM
  3. concentrationThe solution was concentrated with SiO2
  4. customchromatographed through a Redi-Sep pre-packed silica gel column (pure DCM→10% MeOH in DCM w/NH3)
  5. washthe resulting yellow solid was washed with IPA

Sources & evidence

ORD record
ord-36eafd1490194703a0f430e2cbaa1897
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

Loading…