Trifluoromethanesulfonic acid → HCID 59548320, compound

HRID 1812125Notes

Reaction equation

HRID 1812125 reaction equation
[N:1]1([CH2:5][C:6]2[CH:7]=[C:8]([C:21]3[N:26]=[C:25]([CH3:27])[N:24]=[C:23]([N:28](CC4C=CC(OC)=CC=4)CC4C=CC(OC)=CC=4)[N:22]=3)[C:9]([NH:12][C:13]3[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)=[N:10][CH:11]=2)[CH2:4][CH2:3][CH2:2]1.FC(F)(F)S(O)(=O)=O>C(O)(C(F)(F)F)=O>[N:1]1([CH2:5][C:6]2[CH:7]=[C:8]([C:21]3[N:26]=[C:25]([CH3:27])[N:24]=[C:23]([NH2:28])[N:22]=3)[C:9]([NH:12][C:13]3[CH:14]=[N:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)=[N:10][CH:11]=2)[CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 66611155HCID 66611155, compound

Product 1

HCID 59548320HCID 59548320, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-(5-(azetidin-1-ylmethyl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (150 mg, 0.242 mmol) in TFA (2424 μL) was treated with trifluoromethanesulfonic acid (63.5 μL, 0.727 mmol) and stirred at 80° C. for 1 h. The reaction mixture was concentrated and diluted with 100 mL of DCM, added to a separatory funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 2 times with 75 mL of sodium bicarbonate (saturated, aqueous), separated, diluted with a small amount of methanol to make the solution clear, dried over sodium sulfate, and concentrated to give crude product. The crude product was purified via flash chromatography (silica gel) with 100% DCM to 8% 2 M ammonia in MeOH/DCM to give 4-(5-(azetidin-1-ylmethyl)-2-(6-methoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (11 mg, 11.99% yield). 1H NMR (400 MHz, CDCl3) δ 11.75 (s, 1H); 8.90 (d, J=2.35 Hz, 1H); 8.37 (d, J=2.74 Hz, 1H); 8.17 (d, J=2.35 Hz, 1H); 8.08 (dd, J=8.90, 2.64 Hz, 1H); 6.77 (d, J=8.80 Hz, 1H); 3.94 (s, 3H); 3.76 (s, 2H); 3.53 (t, J=7.34 Hz, 4H); 2.53 (s, 3H); 2.28 (quin, J=7.38 Hz, 2H). m/z (ESI, +ve ion) 379.1 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with 100 mL of DCM
  3. additionadded to a separatory funnel
  4. custompartitioned with sodium bicarbonate (saturated, aqueous)
  5. washwashed 2 times with 75 mL of sodium bicarbonate (saturated, aqueous)
  6. customseparated
  7. additiondiluted with a small amount of methanol
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto give crude product
  11. customThe crude product was purified via flash chromatography (silica gel) with 100% DCM to 8% 2 M ammonia in MeOH/DCM

Sources & evidence

ORD record
ord-f7d8e7d5cfd843668f230ce9bdafe451
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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