Sodium Carbonate → tert-butyl 4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamate

HRID 1509310Notes

Reaction equation

HRID 1509310 reaction equation
Br[C:2]1[C:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][C:5]2[NH:10][C:9](=[O:11])[CH2:8][O:7][C:6]=2[N:12]=1.CC1(C)C(C)(C)OB([C:27]2[CH:41]=[CH:40][C:30]([CH2:31][NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:29][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C(=O)(O)[O-].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[O:11]=[C:9]1[CH2:8][O:7][C:6]2[N:12]=[C:2]([C:27]3[CH:41]=[CH:40][C:30]([CH2:31][NH:32][C:33](=[O:39])[O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[CH:29][CH:28]=3)[C:3]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[CH:4][C:5]=2[NH:10]1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 34154424-(tert-Butoxycarbonylaminomethyl)phenylboronic acid, pinacol esterHCID 866836506-bromo-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

Product 1

HCID 67255587tert-butyl 4-(2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamateYield 78.1%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

In a reaction tube was added 6-bromo-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (0.19 g, 0.623 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (0.25 g, 0.750 mmol) in 1,4-Dioxane (10 ml), followed by a solution of sodium carbonate (0.198 g, 1.868 mmol) in water (2.5 ml) to give a suspension. This was degassed followed by the addition of PdCl2(dppf)-CH2Cl2 adduct (0.051 g, 0.062 mmol). The resulting mixture was heated at 80° C. for 20 h. The reaction mixture was cooled down to room temperature and diluted with saturated sodium bicarbonate solution (30 ml) and extracted with ethyl acetate (20 mlX3). The combined organic phase was washed with water, brine and concentrated to give product (0.21 g) used for next step without further purification. LCMS (Method D): RT=1.25 min, M+H+=433.2.

Workup

  1. customto give a suspension
  2. customThis was degassed
  3. temperatureThe reaction mixture was cooled down to room temperature
  4. extractionextracted with ethyl acetate (20 mlX3)
  5. washThe combined organic phase was washed with water, brine
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-c62d6b3890a34cb1adc4aeb9c3d838ad
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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