Cesium carbonate → tert-Butyl 4-(1-ethyl-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamate

HRID 1509328Notes

Reaction equation

HRID 1509328 reaction equation
Br[C:2]1[C:3]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:4][C:5]2[N:10]([CH2:11][CH3:12])[C:9](=[O:13])[CH2:8][O:7][C:6]=2[N:14]=1.CC1(C)C(C)(C)OB([C:29]2[CH:43]=[CH:42][C:32]([CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[CH:31][CH:30]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[CH2:11]([N:10]1[C:9](=[O:13])[CH2:8][O:7][C:6]2[N:14]=[C:2]([C:29]3[CH:43]=[CH:42][C:32]([CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[CH:31][CH:30]=3)[C:3]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:4][C:5]1=2)[CH3:12]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 34154424-(tert-Butoxycarbonylaminomethyl)phenylboronic acid, pinacol esterHCID 866836836-bromo-1-ethyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

Product 1

HCID 86683682tert-Butyl 4-(1-ethyl-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamateYield 65.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

In a 15 mL reaction tube was added 6-bromo-1-ethyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (50 mg, 0.150 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (60.0 mg, 0.180 mmol), and CESIUM CARBONATE (244 mg, 0.750 mmol) in a mixture of 1,4-Dioxane (2814 μl) and water (938 μl) to give a colourless solution. This was degassed by bubbling nitrogen for 15 minutes, followed by the addition of PdCl2(dppf)-CH2Cl2Adduct (24.51 mg, 0.030 mmol) and degassing for a further 5 minutes. The reaction mixture was heated to 50° C. under a nitrogen atmosphere for one hour. LC-MS analysis showed reaction completion. The reaction mixture was allowed to cool to room temperature, diluted with water (5 mL) and extracted into ethyl acetate (3×5 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give an off-white solid. The resulting residue was purified via Biotage (15-85% cyclohexane:EtOAc; 10 g column) to give the title compound (45 mg, 65.3%) as off-white solid. 1H NMR (500 MHz, CDCl3): 7.31-7.27 (6H, m), 7.19-7.18 (2H, d), 7.11-7.10 (2H, d), 4.87 (2H, s), 4.84 (1H, br), 4.27 (2H, s), 4.03-3.98 (2H, q), 1.45 (9H, br), 1.32-1.30 (3H, t).

Workup

  1. customIn a 15 mL reaction tube
  2. customto give a colourless solution
  3. customThis was degassed
  4. customby bubbling nitrogen for 15 minutes
  5. customdegassing for a further 5 minutes
  6. customreaction completion
  7. temperatureto cool to room temperature
  8. extractionextracted into ethyl acetate (3×5 mL)
  9. dry with materialThe combined organic phases were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure
  12. customto give an off-white solid
  13. customThe resulting residue was purified via Biotage (15-85% cyclohexane:EtOAc; 10 g column)

Sources & evidence

ORD record
ord-f61080a91328495baf40e6990b033927
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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