Potassium Carbonate → 7-isoquinolin-4-yl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine

HRID 1943721Notes

Reaction equation

HRID 1943721 reaction equation
Br[C:2]1[CH:11]=[N:10][C:5]2[O:6][CH2:7][CH2:8][NH:9][C:4]=2[CH:3]=1.[C:12]1(B(O)O)[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14][N:13]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCCC1.O>[CH:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([C:2]2[CH:11]=[N:10][C:5]3[O:6][CH2:7][CH2:8][NH:9][C:4]=3[CH:3]=2)=[CH:14][N:13]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 53398519Isoquinolin-1-ylboronic acidHCID 667890617-bromo-1H,2H,3H-pyrido[2,3-b][1,4]oxazine

Product 1

HCID 669367327-isoquinolin-4-yl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazineYield 51%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

Under nitrogen atmosphere, in a 10 ml flask, 7-bromo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine (36.3 mg, 0.169 mmol), isoquinoline boronic acid (44 mg, 0.253 mmol), tetrakis triphenylphosphine palladium (19.5 mg, 0.017 mmol) and potassium carbonate (58.3 mg, 0.423 mmol) were dissolved in a solvent of tetrahydrofuran/water (6/1, 1.4 ml/0.3 ml). The reaction mixture was stirred for 30 minutes at 80° C. using microwave (40 W) device. After cooling to room temperature, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated saline solution. The combined organic layer was dried over anhydrous magnesium sulfate (MgSO4), filtered and evaporated under reduced pressure. The residue was purified by column chromatography on amine silica eluting with a solvent of dichloromethane. The fractions containing the product were collected and evaporated to obtain brown oil (22.6 mg, 51%).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. washthe organic layer was washed with saturated saline solution
  4. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe residue was purified by column chromatography on amine silica eluting with a solvent of dichloromethane
  8. additionThe fractions containing the product
  9. customwere collected
  10. customevaporated

Sources & evidence

ORD record
ord-c064d59bd4454402a17d1f2f925b07ac
Source dataset
uspto-grants-2013_03
Patent number
US08394792B2

Reaction notes

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