Ethyl Acetate → HCID 71144116, compound

HRID 2370883Notes

Reaction equation

HRID 2370883 reaction equation
[NH2:1][C:2]1[C:3]([OH:31])=[CH:4][C:5]([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])=[N:6][CH:7]=1.Cl[C:33](Cl)([O:35]C(=O)OC(Cl)(Cl)Cl)Cl.CCOC(C)=O>C1COCC1.CCCCCC>[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:5]2[N:6]=[CH:7][C:2]3[NH:1][C:33](=[O:35])[O:31][C:3]=3[CH:4]=2)=[O:9])[CH:24]=[CH:23][C:22]=1[O:25][C:26]([F:27])([F:29])[F:28]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 94429TriphosgeneHCID 178508027HCID 178508027, compound

Product 1

HCID 71144116HCID 71144116, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled (−78° C.) and stirred mixture of ((S)-5-amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-4-hydroxypicolinamide (200 mg, 0.00045 mol) in THF (5 mL) was added TEA (0.31 mL, 0.002 mol, Spectrochem, India) and triphosgene (270 mg, 0.0009 mol, Spectrochem, India). The reaction mixture was stirred for 2 h at same temperature, slowly warmed to rt and stirred overnight. After completion of the reaction (monitored by TLC, 50% EtOAc in hexane), the reaction mixture was quenched with sat'd NaHCO3 (5 mL), extracted with EtOAc (10 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, concentrated and purified by column chromatography, silica gel (60-120 mesh) using 50-60% EtOAc in petroleum ether as the eluent, followed by further purification using Prep TLC plates, mobile phase 50% EtOAc in hexanes to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.79 (d, J=7.2 Hz, 1H), 9.00 (s, 1H), 8.53 (d, J=4.4 Hz, 1H), 8.41 (s, 1H), 8.08 (s, 1H), 7.44-7.35 (m, 1H), 7.35-7.31 (m, 3H), 7.26-7.21 (m, 1H), 6.64 (d, J=7.6 Hz, 1H). MS (ESI, positive ion) m/z: 467.2 (M+H).

Workup

  1. stirringThe reaction mixture was stirred for 2 h at same temperature
  2. temperatureslowly warmed to rt
  3. stirringstirred overnight
  4. customthe reaction mixture was quenched with sat'd NaHCO3 (5 mL)
  5. extractionextracted with EtOAc (10 mL×3)
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. custompurified by column chromatography, silica gel (60-120 mesh)
  9. customfollowed by further purification

Sources & evidence

ORD record
ord-efb2bbe76bba4563be5f96b30a42a5b9
Source dataset
uspto-grants-2014_04
Patent number
US08710043B2

Reaction notes

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