Potassium Carbonate → HCID 67255634, compound

HRID 1509189Notes

Reaction equation

HRID 1509189 reaction equation
[O:1]=[C:2]1[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:11][C:4]=2[NH:3]1.Br[CH:37]1[CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:39]([N:3]1[C:2](=[O:1])[CH2:7][O:6][C:5]2[N:8]=[C:9]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:25][CH2:26][CH2:27]4)=[CH:20][CH:19]=3)[C:10]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][C:4]1=2)[CH:37]=[CH2:38]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 78037BromocyclopropaneHCID 67256382HCID 67256382, compound

Product 1

HCID 67255634HCID 67255634, compoundYield 11.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a sealed tube was added tert-butyl 1-(4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)phenyl)cyclobutylcarbamate (100 mg, 0.212 mmol) in DMF to give a brown solution. bromocyclopropane (76.9652 mg, 0.636 mmol) and potassium carbonate were added. The reaction mixture was heated at 80 degree for 16 h. The reaction mixture was then heated under microwave 100 degree for 2 h and 130 degree for 8 h. The reaction mixture was partitioned between dichloromethane (20 ml) and water (20 ml). The organic phase was separated using phase separator and concentrated. The crude product was purified by column (biotage, 25 g) eluted with ethyl acetate/cyclohexane to afford product (12 mg). 1H NMR (500 MHz, CDCl3) 7.17-7.23 (m, 8H), 7.07-7.10 (m, 2H), 5.77-5.84 (m, 1H), 5.18-5.24 (m, 2H), 4.51 (d, 2H), 2.2-2.5 (m, 4H), 1.9-2.0 (m, 1H), 1.69-1.79 (m, 1H), 1.1-1.35 (br, 9H). LCMS (Method A): RT=7.9 min, M+H+=512.17.

Workup

  1. customto give a brown solution
  2. temperatureThe reaction mixture was heated at 80 degree for 16 h
  3. temperatureThe reaction mixture was then heated under microwave 100 degree for 2 h and 130 degree for 8 h
  4. customThe reaction mixture was partitioned between dichloromethane (20 ml) and water (20 ml)
  5. customThe organic phase was separated
  6. concentrationconcentrated
  7. customThe crude product was purified by column (biotage, 25 g)
  8. washeluted with ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-a13651efaf3d43fa828c00a36afc3990
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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