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

HRID 1509305Notes

Reaction equation

HRID 1509305 reaction equation
Br[C:2]1[C:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:4][C:5]2[N:10]([CH3:11])[C:9](=[O:12])[CH2:8][O:7][C:6]=2[N:13]=1.CC1(C)C(C)(C)OB([C:28]2[CH:42]=[CH:41][C:31]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[CH:30][CH:29]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.[Cl-].[Na+].O>[CH3:11][N:10]1[C:9](=[O:12])[CH2:8][O:7][C:6]2[N:13]=[C:2]([C:28]3[CH:42]=[CH:41][C:31]([CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39])=[CH:30][CH:29]=3)[C:3]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[CH:4][C:5]1=2

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 34154424-(tert-Butoxycarbonylaminomethyl)phenylboronic acid, pinacol esterHCID 866836706-bromo-1-methyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

Product 1

HCID 86683669tert-butyl 4-(1-methyl-2-oxo-7-phenyl-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamateYield 72%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

In a 15 mL reaction tube was added 6-bromo-1-methyl-7-phenyl-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (40 mg, 0.125 mmol) and tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (50 mg, 0.150 mmol) in 1,4-dioxane (2 ml), followed by a solution of sodium carbonate (40 mg, 0.3 mmol) in water (0.5 ml) to give a white suspension. This was degassed by bubbling nitrogen for 10 minutes, followed by the addition of [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloromethane adduct (9 mg, 0.013 mmol). The reaction mixture was heated to 80° C. overnight. The reaction mixture was allowed to cool to room temperature, diluted with brine (4 ml) and extracted into ethyl acetate (3×4 ml). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 20:80) to give the desired product as a white solid (40 mg, 72% yield). 1H-NMR (500 MHz, CDCl3) δ 7.27-7.32 (5H, m), 7.25 (1H, s), 7.16-7.20 (2H, m), 7.10 (2H, d), 4.89 (2H, s), 4.81 (1H, br s), 4.26 (2H, br s), 3.39 (3H, s), 1.23 (9H, br s). LCMS (Method D): RT=1.40 min, M+H+=446.20.

Workup

  1. customIn a 15 mL reaction tube
  2. customto give a white suspension
  3. customThis was degassed
  4. customby bubbling nitrogen for 10 minutes
  5. temperatureto cool to room temperature
  6. extractionextracted into ethyl acetate (3×4 ml)
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to dryness under reduced pressure
  10. customThe residue was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 20:80)

Sources & evidence

ORD record
ord-a474af1c72a74d9495a1acfba1033a9b
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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