Trifluoroacetic acid → HCID 178437159, compound

HRID 1811861Notes

Reaction equation

HRID 1811861 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:15]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][N:20]4C3CCCCO3)=[CH:14][C:13]([CH:32]=[CH2:33])=[CH:12][N:11]=2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:15]([C:16]3[N:24]=[C:23]([CH3:25])[N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)=[CH:14][C:13]([CH:32]=[CH2:33])=[CH:12][N:11]=2)=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59548466N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine

Product 1

HCID 178437159HCID 178437159, compoundYield 111%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine (76.3 mg, 0.172 mmol) was dissolved in DCM (2.9 mL) and trifluoroacetic acid (Aldrich, St. Louis, Mo., hplc grade, 0.60 mL, 7.8 mmol) was added via syringe. The reaction was stirred at room temperature for 35 minutes, concentrated, treated with MeOH, and filtered. The solid was washed with Et2O, but was not sufficiently (>95% by HPLC) pure. So, the solid and filtrate were combined, concentrated, treated with 2 N ammonia in MeOH, and concentrated again. The material was treated with Et2O, but this did not precipitate product. So, it was concentrated, treated with water, and filtered. The solid was washed with water, but was still not 95% pure. So, the solid was collected and purified on HPLC (10% to 100% MeCN/water over 30 minutes using a total flow rate of 100 mL/min) to afford N-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)-5-vinylpyridin-2-amine (68.6 mg). MS (ESI pos. ion) m/z 360 (M+H)+. 1H NMR (d6-DMSO) δ 12.70 (s, 1H), 9.98 (s, 1H), 8.65 (s, 1H), 8.55 (d, J=2.54 Hz, 1H), 8.40 (d, J=2.35 Hz, 1H), 8.19 (dd, J=8.8 Hz, 2.74 Hz, 1H), 6.86 (d, J=8.8 Hz, 1H), 6.79 (dd, J=17.5 Hz, 10.9 Hz, 1H), 5.78 (d, J=16.4 Hz, 1H), 5.26 (d, J=11.0 Hz, 1H), 3.85 (s, 3H), 2.86 (s, 3H).

Workup

  1. concentrationconcentrated
  2. additiontreated with MeOH
  3. filtrationfiltered
  4. washThe solid was washed with Et2O
  5. concentrationconcentrated
  6. additiontreated with 2 N ammonia in MeOH
  7. concentrationconcentrated again
  8. additionThe material was treated with Et2O
  9. customthis did not precipitate product
  10. concentrationSo, it was concentrated
  11. additiontreated with water
  12. filtrationfiltered
  13. washThe solid was washed with water
  14. customSo, the solid was collected
  15. custompurified on HPLC (10% to 100% MeCN/water over 30 minutes

Sources & evidence

ORD record
ord-b84c35dd94e24884ae95d6b36cf4e4f5
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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