Triethylamine → 7-(6-hydroxy-7-methoxyquinolin-4-yloxy)-N-(5-methylisoxazol-3-yl)-2,3-dihydrobenzo[b][1,4]oxazine-4-carboxamide

HRID 1712978Notes

Reaction equation

HRID 1712978 reaction equation
[O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[CH:8][C:9]([O:11][C:12]3[C:21]4[C:16](=[CH:17][C:18]([O:23][CH3:24])=[C:19]([OH:22])[CH:20]=4)[N:15]=[CH:14][CH:13]=3)=[CH:10][C:2]1=2.[CH3:25][C:26]1[O:30][N:29]=[C:28]([NH:31][C:32](=O)[O:33]C2C=CC([N+]([O-])=O)=CC=2)[CH:27]=1.C(N(CC)CC)C>C1COCC1>[OH:22][C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][C:18]=1[O:23][CH3:24])[N:15]=[CH:14][CH:13]=[C:12]2[O:11][C:9]1[CH:8]=[CH:7][C:3]2[N:4]([C:32]([NH:31][C:28]3[CH:27]=[C:26]([CH3:25])[O:30][N:29]=3)=[O:33])[CH2:5][CH2:6][O:1][C:2]=2[CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 577371514-(3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yloxy)-7-methoxyquinolin-6-olHCID 594634404-Nitrophenyl 5-methylisoxazol-3-ylcarbamate

Product 1

HCID 426242627-(6-hydroxy-7-methoxyquinolin-4-yloxy)-N-(5-methylisoxazol-3-yl)-2,3-dihydrobenzo[b][1,4]oxazine-4-carboxamideYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A resealable tube was charged with 4-(3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yloxy)-7-methoxyquinolin-6-ol (0.200 g, 0.617 mmol), 4-nitrophenyl 5-methylisoxazol-3-ylcarbamate (0.243 g, 0.925 mmol), and THF (5.0 mL). Triethylamine (0.258 mL, 1.85 mmol) was added, the system was purged with argon, and the tube was sealed. The mixture stirred at 50° C. for 15 h. The reaction mixture was partitioned between ethyl acetate and water. The aqueous phase was separated and extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a yellow-orange oil. This material was purified via column chromatography on silica gel (RediSep 40 g column, eluting with 5% methanol-dichloromethane) to afford a yellow oil. This material was triturated with dichloromethane and filtered to afford 7-(6-hydroxy-7-methoxyquinolin-4-yloxy)-N-(5-methylisoxazol-3-yl)-2,3-dihydrobenzo[b][1,4]oxazine-4-carboxamide (0.104 g, 38% yield) as an off-white solid.

Workup

  1. customthe system was purged with argon
  2. customthe tube was sealed
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. customThe aqueous phase was separated
  5. extractionextracted with ethyl acetate
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford a yellow-orange oil
  11. customThis material was purified via column chromatography on silica gel (RediSep 40 g column, eluting with 5% methanol-dichloromethane)
  12. customto afford a yellow oil
  13. customThis material was triturated with dichloromethane
  14. filtrationfiltered

Sources & evidence

ORD record
ord-44f65c44e0f84e1a858b534d64c89bdc
Source dataset
uspto-grants-2010_09
Patent number
US07795254B2

Reaction notes

Loading…