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

HRID 1621967Notes

Reaction equation

HRID 1621967 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][C:3]=1[O:53][CH3:54].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[CH2:44][CH2:45][N:46]([S:49]([CH3:52])(=[O:51])=[O:50])[CH2:47][CH2:48]3)[CH3:42])=[CH:11][N:10]=2)=[CH:4][C:3]=1[O:53][CH3:54]

Participants

4

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 86647081HCID 86647081, compound

Product 1

HCID 59548251(R)-4-(2-(6-chloro-5-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineYield 78%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (R)-4-(2-(6-chloro-5-methoxypyridin-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 (130 mg, 0.168 mmol) in 3 mL of TFA was treated with 0.1 mL of trifluoromethanesulfonic acid. It was heated in an oil bath at 80° C. for 3 h. The dark solution was concentrated and the residue was treated with ice cube followed by 0.5N NaOH until the pH was about 8. The mixture was extracted with 2×30 mL of EtOAc followed by 2×15 mL of DCM. The combined organic solution was dried and concentrated. The residue was loaded on a silica gel column and eluted with 1 to 10% MeOH in DCM to give (R)-4-(2-(6-chloro-5-methoxypyridin-3-ylamino)-5-(1-(4-(methylsulfonyl)piperazin-1-yl)ethyl)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (70 mg, 78% yield) as a yellow crystalline solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.22 (s, 1H), 8.74 (d, J=2.4 Hz, 1H), 8.44 (d, J=2.2 Hz, 1H), 8.36 (dd, J=10.4, 2.2 Hz, 2H), 7.95 (br., 1H), 7.83 (br., 1H), 3.94 (s, 3H), 3.60 (m, 1H), 3.09 (m, 4H), 2.86 (s, 3H), 2.46 (s, 3H), 2.44 (m, 4H), 1.36 (d, J=6.7 Hz, 3H). m/z (ESI, positive ion) 534.2 (M+H)+.

Workup

  1. concentrationThe dark solution was concentrated
  2. additionthe residue was treated with ice cube
  3. extractionThe mixture was extracted with 2×30 mL of EtOAc
  4. customThe combined organic solution was dried
  5. concentrationconcentrated
  6. washeluted with 1 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-1ea3995e1f4343c1b6b511e178af532e
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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