Ethyl Acetate → 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-7-(propan-2-yloxy)-3,4-dihydropyrido[4,3-f][1,4]oxazepin-5(2H)-one

HRID 577587Notes

Reaction equation

HRID 577587 reaction equation
[CH3:1][C:2]1[C:7]2[C:8](=[O:13])[NH:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[N:4][C:3]=1[O:14][CH:15]([CH3:17])[CH3:16].[H-].[Na+].[CH2:20]([O:27][C:28]1[C:33]([CH2:34]Cl)=[C:32]([CH3:36])[CH:31]=[C:30]([CH3:37])[N:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCOC(C)=O>CN(C=O)C>[CH2:20]([O:27][C:28]1[C:33]([CH2:34][N:9]2[C:8](=[O:13])[C:7]3[C:2]([CH3:1])=[C:3]([O:14][CH:15]([CH3:17])[CH3:16])[N:4]=[CH:5][C:6]=3[O:12][CH2:11][CH2:10]2)=[C:32]([CH3:36])[CH:31]=[C:30]([CH3:37])[N:29]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridineHCID 867238126-methyl-7-(propan-2-yloxy)-3,4-dihydropyrido[4,3-f][1,4]oxazepin-5(2H)-one

Product 1

HCID 867238144-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-7-(propan-2-yloxy)-3,4-dihydropyrido[4,3-f][1,4]oxazepin-5(2H)-oneYield 94,608.203%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-methyl-7-(propan-2-yloxy)-3,4-dihydropyrido[4,3-f][1,4]oxazepin-5(2H)-one (131f, 70 mg, 0.30 mmol) in dry DMF (6 mL) was added NaH (36 mg, 0.90 mmol, 60% in oil) at 0° C. The mixture was stirred at 0° C. for 10 minutes. To the mixture was added 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (Cpd Z, 155 mg, 0.6 mmol). The reaction mixture was stirred at room temperature for 14 hours. To the reaction mixture was added EtOAc (20 mL). The solution was washed with brine (5×15 mL), dried over Na2SO4, and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/EtOAc, 10/1) to give 4-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-6-methyl-7-(propan-2-yloxy)-3,4-dihydropyrido[4,3-f][1,4]oxazepin-5(2H)-one (131 g, 0.14 g, 100%) as a colorless oil.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 14 hours
  2. washThe solution was washed with brine (5×15 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by column chromatography (petroleum ether/EtOAc, 10/1)

Sources & evidence

ORD record
ord-0d3e3b8169bc4b5d979558c0c4ddd47e
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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