Ethyl Acetate → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-2-oxo-2,3-dihydrooxazolo[4,5-b]pyridine-5-carboxamide

HRID 509394Notes

Reaction equation

HRID 509394 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]([NH:10][C@@H:11]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]([F:29])([F:28])[F:27])=[C:21]([F:30])[CH:20]=2)[C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][N:13]=2)=[O:9])[CH:5]=[CH:4][C:3]=1[OH:31].Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl.CCOC(C)=O>C1COCC1>[F:30][C:21]1[CH:20]=[C:19]([C@@H:11]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[CH:14][N:13]=2)[NH:10][C:8]([C:6]2[N:7]=[C:2]3[NH:1][C:33](=[O:35])[O:31][C:3]3=[CH:4][CH:5]=2)=[O:9])[CH:24]=[CH:23][C:22]=1[O:25][C:26]([F:29])([F:27])[F:28]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 94429TriphosgeneHCID 71144459(S)-6-Amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxypicolinamide

Product 1

HCID 71144175(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-2-oxo-2,3-dihydrooxazolo[4,5-b]pyridine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-6-amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxypicolinamide (300 mg, 0.681 mmol) in THF (10 mL) was added TEA (689.4 mg, 0.00068 mmol, S.d fine, India) and triphosgene (242 mg, 0.0008 mmol, Sigma Aldrich, India) at 0° C. The reaction mixture was stirred for 2 h at room temperature. After completion of the reaction, monitored by TLC (TLC eluent: 50% EtOAc in petroleum ether), the reaction mixture was quenched with sat'd NaHCO3 solution and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, concentrated and purified by silica gel (60-120 mesh) column chromatography eluting with 80-100% EtOAc in petroleum ether to afford the title compound as an off white solid. 1H-NMR (400 MHz, DMSO-d6): δ 12.8 (br. s., 1H), 9.46 (d, J=7.2 Hz, 1H), 8.55 (d, J=4.4 Hz, 1H), 7.83-7.77 (m, 3H), 7.57-7.49 (m, 3H), 7.33 (d, J=8.4 Hz, 1H), 6.55 (d, J=6.8 Hz, 1H). MS (ESI, positive ion) m/z: 467.2 (M+H).

Workup

  1. customAfter completion of the reaction
  2. customthe reaction mixture was quenched with sat'd NaHCO3 solution
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. custompurified by silica gel (60-120 mesh) column chromatography
  8. washeluting with 80-100% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-06d0212c7822446fa57918777ed2064c
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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