Benzene, 1-chloro-3-isocyanato- → 7-(6-Oxo-5,6-dihydro-benzo[c][1,8]naphthyridin-1-yloxy)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid (3-chloro-phenyl)-amide

HRID 1029184Notes

Reaction equation

HRID 1029184 reaction equation
[O:1]1[C:6]2[CH:7]=[C:8]([O:11][C:12]3[CH:21]=[CH:20][N:19]=[C:18]4[C:13]=3[C:14]3[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=3[C:16](=[O:22])[NH:17]4)[CH:9]=[CH:10][C:5]=2[NH:4][CH2:3][CH2:2]1.[Cl:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([N:34]=[C:35]=[O:36])[CH:29]=1.CCN(C(C)C)C(C)C>O1CCOCC1.O.CCOC(C)=O>[Cl:27][C:28]1[CH:29]=[C:30]([NH:34][C:35]([N:4]2[C:5]3[CH:10]=[CH:9][C:8]([O:11][C:12]4[CH:21]=[CH:20][N:19]=[C:18]5[C:13]=4[C:14]4[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=4[C:16](=[O:22])[NH:17]5)=[CH:7][C:6]=3[O:1][CH2:2][CH2:3]2)=[O:36])[CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 17968Benzene, 1-chloro-3-isocyanato-HCID 81531DiisopropylethylamineHCID 698108831-(3,4-Dihydro-2H-benzo[1,4]oxazin-7-yloxy)-5H-benzo[c][1,8]naphthyridin-6-one

Product 1

HCID 684033867-(6-Oxo-5,6-dihydro-benzo[c][1,8]naphthyridin-1-yloxy)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid (3-chloro-phenyl)-amideYield 22.9%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 22728543Water ethylacetateSolvent

Procedure

Compound 218 (25 mg, 0.07 mmol), 1-chloro-3-isocyanato-benzene (17 mg, 0.11 mmol), and DIEA (0.04 mL, 0.22 mmol) were dissolved in dioxane (2 mL) and stirred and stirred for 30 minutes at 100° C. in microwave. The reaction mixture was diluted with H2O/EtOAc, and filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was purified via Biotage eluting with a gradient of 50 to 100% EtOAc in hexanes to provide 221 (8 mg, 22% yield) as a tan solid. LC-MS (M+H=499, obsd.=499).

Workup

  1. stirringstirred for 30 minutes at 100° C. in microwave
  2. filtrationfiltered through an Extrelut column
  3. washThe column was washed with EtOAc
  4. concentrationthe filtrate was concentrated
  5. customThe crude product was purified via Biotage
  6. washeluting with a gradient of 50 to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-9b343e5704f2401ba198fbd72b4745e3
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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