Borane → HCID 22648139, compound

HRID 394217Notes

Reaction equation

HRID 394217 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]2[CH2:14][O:15][C:16](=[O:26])[N:17]([C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:25])[C:12]=2[CH:11]=[C:10]([C:27]([N:29]2[CH2:34][CH2:33][N:32]([CH:35]([CH3:37])[CH3:36])[CH2:31][CH2:30]2)=O)[CH:9]=1.B>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]2[CH2:14][O:15][C:16](=[O:26])[N:17]([C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:25])[C:12]=2[CH:11]=[C:10]([CH2:27][N:29]2[CH2:34][CH2:33][N:32]([CH:35]([CH3:37])[CH3:36])[CH2:31][CH2:30]2)[CH:9]=1

Participants

4

Reactant 2

HCID 6331BoraneHCID 10144266HCID 10144266, compound

Product 1

HCID 22648139HCID 22648139, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(4-isopropylpiperazin-1-yl)carbonyl]-1,4-dihydro-2H-3,1-benzoxazin-2-one (31 mg, 0.055 mmol, 1 eq) in THF (0.1 mL) at 0° C. under nitrogen was added a solution of borane in THF (0.1 mL of a 1M solution, 0.1 mmol, 1.8 eq). The mixture was stirred 5 min at 0° C. and then the cooling bath was removed. The mixture was brought to and maintained at reflux for 2 h (twice added 0.1 mL of THF due to solvent loss). The mixture was cooled. To the reaction was added 6N aqueous HCl (0.1 mL) and the mixture was heated in a 70° C. oil bath for 15 min. The mixture was cooled and diluted with CH2Cl2 and aqueous NaHCO3. Aqueous 2N NaOH was added to increase basicity. Mixed and separated the layers. The aqueous layer was back extracted 2× with CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated. The product was purified by flash column chromatography on silica gel giving 5-(2-chlorophenyl)-1-(2,6-dichlorophenyl)-7-[(4-isopropylpiperazin-1-yl)methyl]-1,4-dihydro-2H-3,1-benzoxazin-2-one. Mass spectrum ESI) 544.2 (M+1); 546.2 (M+3).

Workup

  1. customthe cooling bath was removed
  2. temperaturemaintained
  3. temperatureat reflux for 2 h (twice added 0.1 mL of THF due to solvent loss)
  4. temperatureThe mixture was cooled
  5. additionTo the reaction was added 6N aqueous HCl (0.1 mL)
  6. temperaturethe mixture was heated in a 70° C. oil bath for 15 min
  7. temperatureThe mixture was cooled
  8. additiondiluted with CH2Cl2 and aqueous NaHCO3
  9. additionAqueous 2N NaOH was added
  10. temperatureto increase basicity
  11. additionMixed
  12. customseparated the layers
  13. extractionThe aqueous layer was back extracted 2× with CH2Cl2
  14. dry with materialdried over anhydrous Na2SO4
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe product was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-d7f534a7c0e14c39bd37aecf773922fe
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

Loading…