Acetic Acid → tert-butyl(1-(4-(5-oxo-3-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)phenyl)cyclobutyl)carbamate

HRID 1509102Notes

Reaction equation

HRID 1509102 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(=O)C(C3C=CC=CC=3)=CN(C)C)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:32]1(=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][C:34](=O)[CH2:33]1.[C:41](O)(=O)[CH3:42]>>[C:1]([O:5][C:6](=[O:31])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:8]3[N:7]=[C:34]4[CH2:35][CH2:36][CH2:37][CH2:38][C:32](=[O:40])[C:33]4=[CH:10][C:9]=3[C:41]3[CH:42]=[CH:14][CH:13]=[CH:12][CH:17]=3)=[CH:16][CH:17]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 3

HCID 176Acetic AcidHCID 4072367Cycloheptane-1,3-dioneHCID 66719111HCID 66719111, compound

Product 1

HCID 123410895tert-butyl(1-(4-(5-oxo-3-phenyl-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-2-yl)phenyl)cyclobutyl)carbamateYield 24%

Conditions

Temperature
100 °C

Procedure

To a solution of tert-butyl(1-(4-(3-(dimethylamino)-2-phenylacryloyl)phenyl)cyclobutyl)carbamate (119 mg, 0.28 mmol) in acetic acid (1 mL) was added molecular sieves (10 mg) and cycloheptane-1,3-dione (36 μL, 0.42 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), brine (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 (32 mg, 24%). 1H NMR (500 MHz, CDCl3): 8.09 (1H, s), 7.38 (2H, d), 7.30 (2H,d), 7.25-7.24 (3H, m), 7.19-7.17 (2H, m), 5.04 (1H, br s), 3.29 (2H,t), 2.87 (2H, t), 2.60-2.25 (4H, m), 2.07-2.01 (3H, m), 1.99-1.94 (2H, m), 1.84-1.75 (1H, m), 1.42-1.15 (9H, br).

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), brine (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-a9437956fde346fa9bd6cb7e6b5b5941
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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