2H-pyran-3,5(4H,6H)-dione → HCID 86683665, compound

HRID 1509298Notes

Reaction equation

HRID 1509298 reaction equation
CN(C)/[CH:3]=[C:4](\[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)/[C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2([NH:17]C(=O)OC(C)(C)C)[CH2:16][CH2:15][CH2:14]2)=[CH:9][CH:8]=1)=O.[O:32]1[CH2:37][C:36](=O)[CH2:35][C:34](=[O:39])[CH2:33]1.[C:40]([O-:43])(=[O:42])C.[NH4+:44]>C(O)(=O)C>[C:4]([O:43][C:40](=[O:42])[NH:17][C:13]1([C:10]2[CH:11]=[CH:12][C:7]([C:5]3[N:44]=[C:36]4[CH2:37][O:32][CH2:33][C:34](=[O:39])[C:35]4=[CH:3][C:4]=3[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:8][CH:9]=2)[CH2:16][CH2:15][CH2:14]1)([CH3:25])([CH3:5])[CH3:3]

Participants

5

Reactant 3

HCID 3252872H-pyran-3,5(4H,6H)-dioneHCID 517165Ammonium AcetateHCID 66719110HCID 66719110, compound

Product 1

HCID 86683665HCID 86683665, compoundYield 2.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

In a 5 mL reaction tube was added acetic acid (5 ml) followed by (E)-tert-butyl 1-(4-(3-(dimethylamino)-2-phenylacryloyl)phenyl)cyclobutylcarbamate (750 mg, 1.783 mmol), 2H-pyran-3,5(4H,6H)-dione (305 mg, 2.68 mmol), ammonium acetate (412 mg, 5.35 mmol) and molecular sieves (100 mg) to give a brown suspension. The reaction mixture was stirred at 100° C. under a nitrogen atmosphere for 2 hours, then allowed to cool to room temperature and concentrated under reduced pressure. The residue was partitioned between water (10 mL) and dichloromethane (10 mL) and decanted from the molecular sieves. The layers were separated and the aqueous phase extracted into dichloromethane (2×10 mL). The combined organic phases were washed with saturated sodium bicarbonate solution (2×10 mL), brine (10 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a yellow/brown solid. This was purified twice by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 93:7 to 60:40) and then preparative HPLC (Method F) to give the desired product as a white solid (12 mg, 1.4% yield). 1H-NMR (500 MHz, CDCl3) δ 8.29 (1H, s), 7.16-7.41 (9H, m), 5.05 (2H, s), 5.02 (1H, br s), 4.44 (2H, s), 2.21-2.66 (4H, br m), 2.01-2.16 (1H, m), 1.74-1.88 (1H, m), 1.10-1.50 (9H, br m).

Workup

  1. customIn a 5 mL reaction tube
  2. customto give a brown suspension
  3. temperatureto cool to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between water (10 mL) and dichloromethane (10 mL)
  6. customdecanted from the molecular sieves
  7. customThe layers were separated
  8. extractionthe aqueous phase extracted into dichloromethane (2×10 mL)
  9. washThe combined organic phases were washed with saturated sodium bicarbonate solution (2×10 mL), brine (10 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated to dryness under reduced pressure
  13. customto give a yellow/brown solid
  14. customThis was purified twice by Biotage chromatography (cyclohexane:ethyl acetate, gradient elution from 93:7 to 60:40)

Sources & evidence

ORD record
ord-ba1e59d3665041d89b645e74a5da7f8c
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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