Trifluoroacetic acid → HCID 67034300, compound

HRID 539135Notes

Reaction equation

HRID 539135 reaction equation
[P:1]([O:13][CH2:14][N:15]1[CH:19]=[N:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[N:28][N:29]4[CH:34]=[CH:33][C:32]([N:35]5[C@@H:39]([C:40]6[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=6)[CH2:38][O:37][C:36]5=[O:46])=[N:31][C:30]=34)=[CH:22][C:21]=2[F:47])=[N:16]1)([O:8]C(C)(C)C)([O:3]C(C)(C)C)=[O:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[P:1]([OH:3])([OH:8])([O:13][CH2:14][N:15]1[CH:19]=[N:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[N:28][N:29]4[CH:34]=[CH:33][C:32]([N:35]5[C@@H:39]([C:40]6[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=6)[CH2:38][O:37][C:36]5=[O:46])=[N:31][C:30]=34)=[CH:22][C:21]=2[F:47])=[N:16]1)=[O:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 131731964HCID 131731964, compound

Product 1

HCID 67034300HCID 67034300, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (S)-di-tert-butyl (3-(2-fluoro-4-(5-(2-oxo-4-(pyridin-2-yl)oxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methyl phosphate (50 mg, 0.075 mmol) in DCM (0.5 mL) cooled to 0° C. was added TFA (0.1 mL) and the reaction stirred at 0° C. for 1 hour. The reaction was concentrated under vacuum and azeotroped with DCM/Hexanes. The remaining material was taken up in water. The aqueous layer was made basic (pH 9) by the addition of saturated NaHCO3. HCl (0.1 N) was then slowly added to the solution to adjust the pH to 2. The precipitated solid was collected by filtration, washed with acetone and diethyl ether, and dried under vacuum to give (S)-(3-(2-fluoro-4-(5-(2-oxo-4-(pyridin-2-yl)oxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methyl dihydrogen phosphate (22 mg, 53% yield) as a yellow solid. 1H-NMR (400 MHz, DMSO-d6) δ 9.11 (d, J=7.6 Hz, 1H), 8.79 (s, 1H), 8.73 (s, 1H), 8.52 (d, J=4.0 Hz, 1H), 7.99 (m, 2H), 7.84 (t, J=7.6 Hz, 1H), 7.72 (m, 3H), 7.31 (t, J=6.4 Hz, 1H), 6.06 (d, J=6.0 Hz, 1H), 5.95 (d, J=10.8 Hz, 2H), 4.91 (t, J=8.4 Hz, 1H), 4.32 (dd, J=8.4 Hz, 2.8 Hz, 1H).

Workup

  1. concentrationThe reaction was concentrated under vacuum
  2. customazeotroped with DCM/Hexanes
  3. additionby the addition of saturated NaHCO3
  4. additionHCl (0.1 N) was then slowly added to the solution
  5. filtrationThe precipitated solid was collected by filtration
  6. washwashed with acetone and diethyl ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-42cff8788f174c6f9ddd48921499cae6
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

Loading…