Diisopropylethylamine → 1-[4-(4-Fluoro-2-trifluoromethyl-benzoyl)-3,4-dihydro-2H-benzo[1,4]oxazin-7-yloxy]-5H-benzo[c][1,8]naphthyridin-6-one

HRID 1029182Notes

Reaction equation

HRID 1029182 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.[F:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[C:30]([C:37]([F:40])([F:39])[F:38])[CH:29]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[F:27][C:28]1[CH:36]=[CH:35][C:31]([C:32]([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:33])=[C:30]([C:37]([F:38])([F:39])[F:40])[CH:29]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6056804-Fluoro-2-(trifluoromethyl)benzoyl chlorideHCID 698108831-(3,4-Dihydro-2H-benzo[1,4]oxazin-7-yloxy)-5H-benzo[c][1,8]naphthyridin-6-one

Product 1

HCID 581683171-[4-(4-Fluoro-2-trifluoromethyl-benzoyl)-3,4-dihydro-2H-benzo[1,4]oxazin-7-yloxy]-5H-benzo[c][1,8]naphthyridin-6-oneYield 37.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Compound 218 (50 mg, 0.14 mmol), 4-fluoro-2-trifluoromethyl-benzoyl chloride (49 mg, 0.22 mmol), and DIEA (0.07 mL, 0.43 mmol) were dissolved in dioxane (2 mL) and stirred for 1 h at room temperature. The reaction was quenched with H2O, diluted with 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 0 to 100% EtOAc in hexanes to provide 219 (28 mg, 36% yield) as a tan solid. LC-MS (M+H=536, obsd.=536).

Workup

  1. customThe reaction was quenched with H2O
  2. additiondiluted with EtOAc
  3. filtrationfiltered through an Extrelut column
  4. washThe column was washed with EtOAc
  5. concentrationthe filtrate was concentrated
  6. customThe crude product was purified via Biotage
  7. washeluting with a gradient of 0 to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-311809829cac4e0fbf0367e19400e909
Source dataset
uspto-grants-2014_05
Patent number
US08735584B2

Reaction notes

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