Trifluoromethanesulfonic acid → (R)-4-(2-(6-chloropyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621893Notes

Reaction equation

HRID 1621893 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([C:15]3[N:20]=[C:19]([CH3:21])[N:18]=[C:17]([N:22](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:16]=3)=[CH:13][C:12]([C@H:41]([N:43]3[CH2:48][CH2:47][N:46]([S:49]([CH3:52])(=[O:51])=[O:50])[CH2:45][CH2:44]3)[CH3:42])=[CH:11][N:10]=2)=[CH:4][CH:3]=1.FC(F)(F)S(O)(=O)=O>C(O)(C(F)(F)F)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9]2[C:14]([C:15]3[N:20]=[C:19]([CH3:21])[N:18]=[C:17]([NH2:22])[N:16]=3)=[CH:13][C:12]([C@H:41]([N:43]3[CH2:48][CH2:47][N:46]([S:49]([CH3:52])(=[O:50])=[O:51])[CH2:45][CH2:44]3)[CH3:42])=[CH:11][N:10]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 86647072(R)-4-(2-(6-chloropyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 59548186(R)-4-(2-(6-chloropyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 62.5%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
25 °C

Procedure

A brown solution of (R)-4-(2-(6-chloropyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (125.0 mg, 0.168 mmol) and trifluoromethanesulfonic acid (0.15 mL, 1.689 mmol) in TFA (1.5 mL) was stirred at 75° C. for 1.5 h. The mixture was subsequently cooled to 25° C. and concentrated in vacuo. The residue was taken up in CH2Cl2 (50 mL), and the resulting solution was washed with saturated aqueous sodium bicarbonate (40 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (2×30 mL). All organic layers were then combined, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0 to 10% MeOH/CH2Cl2) furnished (R)-4-(2-(6-chloropyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (52.8 mg, 0.105 mmol, 62.4% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.16 (s, 1H), 8.88 (d, J=2.7 Hz, 1H), 8.74 (d, J=2.5 Hz, 1H), 8.48 (dd, J=8.7, 2.8 Hz, 1H), 8.35 (d, J=2.3 Hz, 1H), 7.45 (d, J=8.8 Hz, 1H), 3.59 (q, J=6.8 Hz, 1H), 3.09 (t, J=4.5 Hz, 4H), 2.86 (s, 3H), 2.56 (br. s., 2H), 2.46 (s, 3H), 2.41-2.45 (m, 2H), 1.36 (d, J=6.7 Hz, 3H). m/z (ESI, +ve) 504.1 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. washthe resulting solution was washed with saturated aqueous sodium bicarbonate (40 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (2×30 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customChromatographic purification of the residue (silica gel, 0 to 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-71427fb7cae240e98b31e89765d7168b
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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