Ethyl Acetate → (S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-2-oxo-1,2-dihydrooxazolo[5,4-b]pyridine-5-carboxamide

HRID 509401Notes

Reaction equation

HRID 509401 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]([NH:11][C@@H:12]([C:20]2[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[C:22]([F:31])[CH:21]=2)[C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][N:14]=2)=[O:10])=[N:6][C:7]=1[OH:8].Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl.CCOC(C)=O>C1COCC1.CCCCCC>[F:31][C:22]1[CH:21]=[C:20]([C@@H:12]([C:13]2[C:18]([F:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[NH:11][C:9]([C:5]2[N:6]=[C:7]3[O:8][C:33](=[O:35])[NH:1][C:2]3=[CH:3][CH:4]=2)=[O:10])[CH:25]=[CH:24][C:23]=1[O:26][C:27]([F:28])([F:30])[F:29]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 94429TriphosgeneHCID 178507640HCID 178507640, compound

Product 1

HCID 71144268(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-2-oxo-1,2-dihydrooxazolo[5,4-b]pyridine-5-carboxamide

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.), stirred mixture of (S)-5-amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-6-hydroxypicolinamide (400 mg, 0.00098 mol) in THF (4 mL) was added TEA (1.31 mL, 0.0090 mol, Spectrochem, India) and triphosgene (323 mg, 0.0010 mol, Spectrochem, India) in one lot and the reaction mixture was stirred for 2 h at the same temperature. The reaction was slowly warmed to room temperature overnight. After completion of the reaction (monitored by TLC, 50% EtOAc in hexane), the reaction mixture was quenched with water (2 mL) and extracted with EtOAc (2 mL×3). The combined organic layers were dried over anhydrous sodium sulfate and purified by column chromatography, silica (60-120 mesh) using 50-60% EtOAc in petroleum ether as an eluent, and subsequently purified further using Prep TLC plates, mobile phase 50% EtOAc in hexane to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ: 12.40 (s, 1H), 9.53 (d, J=7.2 Hz, 1H), 8.59 (d, J=4.4 Hz, 1H), 7.90-7.80 (m, 2H), 7.61-7.53 (m, 4H), 7.35 (d, J=8.8 Hz, 1H), 6.54 (d, J=7.2 Hz, 1H). MS (ESI, positive ion) m/z: 467.1 (M+H).

Workup

  1. stirringthe reaction mixture was stirred for 2 h at the same temperature
  2. temperatureThe reaction was slowly warmed to room temperature overnight
  3. customthe reaction mixture was quenched with water (2 mL)
  4. extractionextracted with EtOAc (2 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. custompurified by column chromatography, silica (60-120 mesh)
  7. customsubsequently purified further

Sources & evidence

ORD record
ord-5a3b86e9e4e84cb98c905dcdda3ef1e1
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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