3-Amino-5,5-dimethyl-2-cyclohexen-1-one → HCID 123241448, compound

HRID 1509097Notes

Reaction equation

HRID 1509097 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[C:19]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20]N(C)C)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:32][C:33]1[CH2:38][C:37]([CH3:40])([CH3:39])[CH2:36][C:35](=[O:41])[CH:34]=1>C(O)(=O)C>[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:20][C:34]4[C:35](=[O:41])[CH2:36][C:37]([CH3:40])([CH3:39])[CH2:38][C:33]=4[N:32]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 1366803-Amino-5,5-dimethyl-2-cyclohexen-1-oneHCID 66719111HCID 66719111, compound

Product 1

HCID 123241448HCID 123241448, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl(1-(4-(3-(dimethylamino)-2-phenylacryloyl)phenyl)cyclobutyl)carbamate (166 mg, 0.40 mmol) in acetic acid (1 mL) was added molecular sieves (10 mg) and 3-amino-5,5-dimethylcyclohex-2-enone (82 mg, 0.59 mmol) under nitrogen. The resulting mixture was heated at 100° C. for 2 h. After cooled down to room temperature, the mixture was partitioned between water (10 mL) and dichloromethane (10 mL). The layers were separated and the aqueous phase extracted into dichloromethane (2×10 mL). The combined organic phases were washed with saturated NaHCO3 solution (20 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 20% EtOAc in hexane) to give the title compound (80 mg, 41%). 1H NMR (500 MHz, CDCl3): 8.27 (1H, s), 7.37 (2H, d), 7.30 (2H, d), 7.25-7.24 (3H, m), 7.19-7.17 (2H, m), 5.06 (1H, br s), 3.13 (2H, s), 2.59 (2H, s), 2.55-2.25 (4H, m), 2.09-2.01 (1H, m), 1.82-1.77 (1H, m), 1.44-1.15 (9H, br), 1.17 (6H, s).

Workup

  1. temperatureAfter cooled down to room temperature
  2. customthe mixture was partitioned between water (10 mL) and dichloromethane (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase extracted into dichloromethane (2×10 mL)
  5. washThe combined organic phases were washed with saturated NaHCO3 solution (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness under reduced pressure
  9. customThe resulting residue was purified by Biotage silica gel chromatography (gradient 0 to 20% EtOAc in hexane)

Sources & evidence

ORD record
ord-32376b07deec4147a4d04adc2eea3695
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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