3-Bromo-4-fluorobenzaldehyde → 4-(3-bromo-4-fluorophenyl)-1-methyl-4,9-dihydro-1 H-isoxazolo[3,4-b]pyrano[4,3-e]pyridine-3,5(6H,8H)-dione

HRID 1837099Notes

Reaction equation

HRID 1837099 reaction equation
[NH2:1][C:2]1[N:3]([CH3:8])[O:4][C:5](=[O:7])[CH:6]=1.[Br:9][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][C:17]=1[F:18])[CH:13]=O.[O:19]1[CH2:24][C:23](=O)[CH2:22][C:21](=[O:26])[CH2:20]1>C(O)C>[Br:9][C:10]1[CH:11]=[C:12]([CH:13]2[C:22]3[C:21](=[O:26])[CH2:20][O:19][CH2:24][C:23]=3[NH:1][C:2]3[N:3]([CH3:8])[O:4][C:5](=[O:7])[C:6]2=3)[CH:15]=[CH:16][C:17]=1[F:18]

Participants

5

Reactant 3

HCID 1736043-Bromo-4-fluorobenzaldehydeHCID 3252872H-pyran-3,5(4H,6H)-dioneHCID 234974983-Amino-2-methyl-2,5-dihydro-1,2-oxazol-5-one

Product 1

HCID 101574984-(3-bromo-4-fluorophenyl)-1-methyl-4,9-dihydro-1 H-isoxazolo[3,4-b]pyrano[4,3-e]pyridine-3,5(6H,8H)-dioneYield 22.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The product from Example 45A (0.11 g, 1 mmol), 3-bromo-4-fluoro-benzaldehyde(0.2 g, 1 mmol), and 2H-pyran-3,5(4H,6H)-dione (0.11 g, 1 mmol) in ethyl alcohol (3 mL) were heated at 80° C. for 2 days in a sealed tube. The reaction mixture was allowed to cool to ambient temperature and was evaporated under reduced pressure. The residue was chromatographed eluting with 5% ethanol/dichloromethane to provide the title compound as a white solid (0.09 g). 1H NMR (300 MHz, DMSO-d6) δ 3.27 (s, 3H), 4.05 (s, 2H), 4.57 (q, 2H), 4.78 (s, 1H), 7.28 (m, 2H), 7.54 (d, 1H), 10.77 (s, 1H); MS (ESI−) m/z 395 (M−H)−; Anal. Calcd for C16H12BrFN2O4: C, 48.63; H, 3.06; N, 7.09.

Workup

  1. customwas evaporated under reduced pressure
  2. customThe residue was chromatographed
  3. washeluting with 5% ethanol/dichloromethane

Sources & evidence

ORD record
ord-c8b7f31a0a8f46b0a44b9f5aee42f7a9
Source dataset
uspto-grants-2004_08
Patent number
US06780872B2

Reaction notes

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