Trifluoroacetic acid → HCID 178515773, compound

HRID 1890283Notes

Reaction equation

HRID 1890283 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([OH:17])=[N:8][C:9]=1[NH:10][CH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)([O-])=O.[CH:18](OC)(OC)OC.FC(F)(F)C(O)=O>[Ni].CO>[O:14]1[CH2:15][CH2:16][CH:11]([N:10]2[C:9]3=[N:8][C:7]([OH:17])=[CH:6][CH:5]=[C:4]3[N:1]=[CH:18]2)[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 9005Trimethyl orthoformateHCID 178526709HCID 178526709, compound

Product 1

HCID 178515773HCID 178515773, compoundYield 15.5%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

5-Nitro-6-(tetrahydro-2H-pyran-4-ylamino)pyridin-2-ol (0.173 g, 0.723 mmol) and methanol (160 mL) were stirred at 25° C. for 4 h with excess Raney nickel and under an atmosphere of hydrogen. After 4 h the solution was filtered by vacuum filtration through Celite® and the solvent was removed under reduced pressure. The intermediate 5-amino-6-(tetrahydro-2H-pyran-4-ylamino)pyridin-2-ol was then taken up in trimethyl orthoformate (20.0 mL, 183 mmol), and trifluoroacetic acid (0.05 ml, 0.649 mmol) was added. The solution was stirred at room temperature overnight. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC to give the title compound (0.0246 g). LCMS m/z=220.0 [M+H]+; 1H NMR (400 MHz, acetonitrile-d3) δ ppm 2.10-2.20 (m, 2H), 2.31 (qd, J1=12.4 Hz, J2=4.7 Hz, 2H), 3.59 (td, J1=12.0 Hz, J2=1.9 Hz, 2H), 4.11 (dd, J1=11.8 Hz, J2=4.5 Hz, 2H), 4.80-4.90 (m, 1H), 6.98 (d, J=8.9 Hz, 1H), 8.18 (d, J=8.9 Hz, 1H), 8.56 (s, 1H).

Workup

  1. filtrationAfter 4 h the solution was filtered by vacuum filtration through Celite®
  2. customthe solvent was removed under reduced pressure
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-adcd686e61ae4875ba21a7f574233ca8
Source dataset
uspto-grants-2013_08
Patent number
US08507473B2

Reaction notes

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