Cesium carbonate → (S)-di-tert-butyl (3-(2-fluoro-4-(5-(4-(5-fluoropyridin-2-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methyl phosphate

HRID 539126Notes

Reaction equation

HRID 539126 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[N:15][N:16]3[CH:21]=[CH:20][C:19]([N:22]4[C@@H:26]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=5)[CH2:25][O:24][C:23]4=[O:34])=[N:18][C:17]=23)[CH:5]=[CH:6][C:7]=1[C:8]1[N:12]=[CH:11][NH:10][N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[P:41]([O:53][CH2:54]Cl)([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42]>CN(C=O)C.CCOC(C)=O>[P:41]([O:53][CH2:54][N:10]1[CH:11]=[N:12][C:8]([C:7]2[CH:6]=[CH:5][C:4]([C:13]3[CH:14]=[N:15][N:16]4[CH:21]=[CH:20][C:19]([N:22]5[C@@H:26]([C:27]6[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=6)[CH2:25][O:24][C:23]5=[O:34])=[N:18][C:17]=34)=[CH:3][C:2]=2[F:1])=[N:9]1)([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])([O:48][C:49]([CH3:50])([CH3:51])[CH3:52])=[O:42]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 178519150HCID 178519150, compound

Product 1

HCID 131731963(S)-di-tert-butyl (3-(2-fluoro-4-(5-(4-(5-fluoropyridin-2-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methyl phosphateYield 28.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-3-(3-(3-fluoro-4-(1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-4-(5-fluoropyridin-2-yl)oxazolidin-2-one (0.66 g, 1.4 mmol) in DMF (10 mL) was added cesium carbonate (0.47 g, 1.4 mmol) followed by di-tert-butyl chloromethyl phosphate (1.1 g, 4.3 mmol) and the reaction mixture was stirred overnight at ambient temperature, then diluted with EtOAc (100 mL). The organic layer was washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was chromatographed twice on silica gel using EtOAc as eluent to yield (S)-di-tert-butyl (3-(2-fluoro-4-(5-(4-(5-fluoropyridin-2-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,4-triazol-1-yl)methyl phosphate (0.27 g, 0.40 mmol, 28% yield).

Workup

  1. washThe organic layer was washed with water and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was chromatographed twice on silica gel

Sources & evidence

ORD record
ord-2b80775c0ffa47bea698411f43728cc2
Source dataset
uspto-grants-2014_10
Patent number
US08865726B2

Reaction notes

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