Dichloromethane → HCID 90408950, compound

HRID 589051Notes

Reaction equation

HRID 589051 reaction equation
Br[C:2]1[C:11]2[O:10][CH2:9][CH:8]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][NH:13]3)[N:7]3[C:18](=[O:20])[NH:19][C:5]([C:6]=23)=[CH:4][CH:3]=1.[CH3:21][C:22]1[C:26](B(O)O)=[C:25]([CH3:30])[O:24][N:23]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O>[CH3:21][C:22]1[C:26]([C:2]2[C:11]3[O:10][CH2:9][CH:8]([CH:12]4[CH2:17][CH2:16][CH2:15][CH2:14][NH:13]4)[N:7]4[C:18](=[O:20])[NH:19][C:5]([C:6]=34)=[CH:4][CH:3]=2)=[C:25]([CH3:30])[O:24][N:23]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343463,5-Dimethylisoxazole-4-boronic acidHCID 90410414HCID 90410414, compound

Product 1

HCID 90408950HCID 90408950, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The 7-bromo-4-piperidin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (0.025 g, 0.074 mmol) of Step 2 was combined with (3,5-dimethylisoxazol-4-yl)boronic acid (0.016 g, 0.11 mmol) in 1,4-dioxane (3.0 mL) with potassium carbonate (0.02 g, 0.15 mmol) in water (0.38 mL) and was degassed with nitrogen. The catalyst [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.006 g, 0.007 mmol) was added and the reaction was heated in a sealed tube to 100° C. After stirring for 2 h the reaction was allowed to cool to room temperature and was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated to give the crude product as a dark oil. The product was purified by prep HPLC on a C-18 column eluting a water:acetonitrile gradient buffered at pH 2 with TFA to give 7-(3,5-dimethylisoxazol-4-yl)-4-piperidin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one as two fractions.

Workup

  1. customwas degassed with nitrogen
  2. temperatureto cool to room temperature
  3. customwas partitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give the crude product as a dark oil
  8. customThe product was purified by prep HPLC on a C-18 column
  9. washeluting a water

Sources & evidence

ORD record
ord-499e8a10204146939a9f7578b6f17d21
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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