Potassium Carbonate → HCID 67256231, compound

HRID 1509218Notes

Reaction equation

HRID 1509218 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.C(=O)([O-])[O-].[K+].[K+].[CH3:42][S:43][CH2:44]Cl>CN(C)C=O.C(=O)(O)[O-].[Na+]>[CH3:42][S:43][CH2:44][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

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 16916Chloromethyl methyl sulfideHCID 67256382HCID 67256382, compound

Product 1

HCID 67256231HCID 67256231, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

In a 15 mL reaction 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 (150 mg, 0.318 mmol), potassium carbonate (132 mg, 0.954 mmol) and chloromethyl methyl sulfide (0.079 mL, 0.954 mmol) in anhydrous N,N-dimethylformamide (2 mL) to give a yellow suspension. The reaction mixture was heated to 80° C. under a nitrogen atmosphere for 2 hours, then allowed to cool to room temperature, diluted with saturated sodium bicarbonate solution (10 mL) and extracted into dichloromethane (3×5 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a yellow oil. This was purified by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 90:10 to 80:20) to give the desired product as a white solid (75 mg, 44% yield). 1H-NMR (500 MHz, CDCl3) δ 7.43 (1H, s), 7.23-7.35 (7H, m), 7.19-7.23 (2H, m), 5.09 (3H, br s), 4.94 (2H, s), 2.30-2.55 (4H, m), 2.26 (3H, s), 2.00-2.15 (1H, m), 1.75-1.90 (1H, m), 1.10-1.50 (9H, br s). LCMS (Method A) RT=7.42 min, M+H+=532.14.

Workup

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

Sources & evidence

ORD record
ord-0a5dff33fa2548e79be2d46deb2f9431
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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