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

HRID 1029183Notes

Reaction equation

HRID 1029183 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][C:31]([N:34]=[C:35]=[O:36])=[CH:30][CH:29]=1.CCN(C(C)C)C(C)C>O1CCOCC1.O.CCOC(C)=O>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([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:30][CH:29]=1

Participants

6

Reactant 3

HCID 76934-Chlorophenyl IsocyanateHCID 81531DiisopropylethylamineHCID 698108831-(3,4-Dihydro-2H-benzo[1,4]oxazin-7-yloxy)-5H-benzo[c][1,8]naphthyridin-6-one

Product 1

HCID 684034037-(6-Oxo-5,6-dihydro-benzo[c][1,8]naphthyridin-1-yloxy)-2,3-dihydro-benzo[1,4]oxazine-4-carboxylic acid (4-chloro-phenyl)-amideYield 73%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 22728543Water ethylacetateSolvent

Procedure

Compound 218 (50 mg, 0.14 mmol), 1-chloro-4-isocyanato-benzene (33 mg, 0.22 mmol), and DIEA (0.07 mL, 0.43 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. The resulting precipitate was filtered, washed with EtOAc, and dried under vacuum to provide 220 (51 mg, 71% yield) as a tan solid. LC-MS (M+H=499, obsd.=499).

Workup

  1. stirringstirred for 30 minutes at 100° C. in microwave
  2. filtrationThe resulting precipitate was filtered
  3. washwashed with EtOAc
  4. customdried under vacuum

Sources & evidence

ORD record
ord-1081b4fa19644ab98d08d483cb3d4952
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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