Acetic Acid → HCID 20729738, compound

HRID 352165Notes

Reaction equation

HRID 352165 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:4]=1[C:10]1[C:14]([C:15](Cl)=[O:16])=[C:13]([CH3:18])[O:12][N:11]=1.C([N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])C.[C:26](O)(=O)[CH3:27]>>[C:24]1([NH:21][CH2:22][CH2:23][C@@H:27]2[CH2:26][CH2:3][CH2:4][C@H:10]([NH:11][C:15]([C:14]3[C:10]([C:4]4[C:5]([F:9])=[CH:6][CH:7]=[CH:8][C:3]=4[Cl:2])=[N:11][O:12][C:13]=3[CH3:18])=[O:16])[CH2:14]2)[CH:25]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27365813-(2-Chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride

Product 1

HCID 20729738HCID 20729738, compound

Procedure

A compound from preparation 91 (53 mg; 0.166 mmol) was dissolved in excess, neat acetic acid saturated with HCl(g) (2 mL). After 30 min of stirring at room temperature, in air, the solution was concentrated to dryness by rotary evaporation. Acetic acid was removed from the resultant solid by consecutive dissolution in, and drying from, acetonitrile (thrice) and then diethyl ether (twice). The resulting white powder was dissolved in anhydrous dichloromethane (8 mL) under a nitrogen atmosphere. First was added 3-(2-chloro-6-fluoro-phenyl)-5-methylisoxazole-4-carbonyl chloride (50.2 mg; 0.183 mmol; 1.1 equiv), and then 4-N,N-dimethylaminopyridine (2 mg; 0.017 mmol; 0.1 equiv) and finally triethylamine (94 μL; 0.667 mmol; 4 equiv). The reaction solution was stirred overnight, then quenched with saturated NaHCO3(aq), then extracted with dichloromethane (twice). The organic layer was washed with saturated NaCl(aq) (once), dried with Na2SO4(s), filtered, and concentrated to dryness by rotary evaporation. The resulting product was dissolved in dichloromethane and purified by radial chromatography on a 2 mm thick silica gel rotor. A dichloromethane mobile phase was followed by a 5% tetrahydrofuran/dichloromethane (v/v) mobile phase. An off-white solid (66 mg; 87%) was obtained. TOF-MS(ES) calc'd: [M+H]+=456.1854 m/z.

Workup

  1. customA compound from preparation 91 (53 mg; 0.166 mmol)
  2. concentrationthe solution was concentrated to dryness by rotary evaporation
  3. customAcetic acid was removed from the resultant solid
  4. dissolutionby consecutive dissolution in, and
  5. dry with materialdrying from, acetonitrile (thrice)
  6. dissolutionThe resulting white powder was dissolved in anhydrous dichloromethane (8 mL) under a nitrogen atmosphere
  7. stirringThe reaction solution was stirred overnight
  8. customquenched with saturated NaHCO3(aq)
  9. extractionextracted with dichloromethane (twice)
  10. washThe organic layer was washed with saturated NaCl(aq) (once),
  11. dry with materialdried with Na2SO4(s)
  12. filtrationfiltered
  13. concentrationconcentrated to dryness by rotary evaporation
  14. dissolutionThe resulting product was dissolved in dichloromethane
  15. custompurified by radial chromatography on a 2 mm thick silica gel rotor
  16. customAn off-white solid (66 mg; 87%) was obtained

Sources & evidence

ORD record
ord-a6c2f9b0e84f493b88352515389a3dcc
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

Loading…