tert-Butyl acrylate → 3-(3-Oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid tert-butyl ester

HRID 1362360Notes

Reaction equation

HRID 1362360 reaction equation
Br[C:2]1[CH:13]=[N:12][C:5]2[NH:6][CH2:7][C:8](=[O:11])[NH:9][CH2:10][C:4]=2[CH:3]=1.[C:14]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])(=[O:17])[CH:15]=[CH2:16].C(N(C(C)C)CC)(C)C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]([O:18][C:14](=[O:17])[CH:15]=[CH:16][C:2]1[CH:13]=[N:12][C:5]2[NH:6][CH2:7][C:8](=[O:11])[NH:9][CH2:10][C:4]=2[CH:3]=1)([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 3

HCID 15458tert-Butyl acrylateHCID 81531DiisopropylethylamineHCID 592776207-Bromo-1,2,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-3-one

Product 1

HCID 669672043-(3-Oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid tert-butyl esterYield 55.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

7-Bromo-1,2,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-3-one (145 mg, 0.6 mmol) and tert-butyl acrylate (307 mg, 2.4 mmol) were dissolved in DMF (3 mL) and the reaction vessel was purged with argon for 5 min. Tri-σ-tolylphosphine (37 mg, 0.12 mmol) and palladium acetate (14 mg, 0.06 mmol) were added and the solution was degassed with argon. Diisopropylethylamine (0.23 mL, 1.32 mmol) was added and the solution was degassed with argon, sealed and heated to 90° C. for 16 h. The reaction was cooled to room temperature and filtered through a bed of celite. The filter cake was washed with ethyl acetate (50 mL) and the filtrate was washed with H2O (5 mL) and brine (5 mL), dried over MgSO4 and concentrated to a brown oil. The oil was subjected to silica gel chromatography (5% MeOH./CH2Cl2 to 10% MeOH/CH2Cl2) to yield the title compound as a yellow solid (96 mg, 52%). 1H NMR (300 MHz, DMSO-d6) 8.18 (t, J=5.7 Hz, 1H), 8.07 (d, J=2.1 Hz, 1H), 7.37 (d, J=15.8 Hz, 1H), 7.35 (t, J=5.3 Hz, 1H), 6.24 (d, J=15.8 Hz, 1H), 4.28 (d, J=5.7 Hz, 2H), 3.98 (d, J=5.1 Hz, 2H), 1.45 (s, 9H); ESI MS m/z 290 [C15H19N3O3+H]+.

Workup

  1. customthe reaction vessel was purged with argon for 5 min
  2. customthe solution was degassed with argon
  3. customthe solution was degassed with argon
  4. customsealed
  5. temperatureThe reaction was cooled to room temperature
  6. filtrationfiltered through a bed of celite
  7. washThe filter cake was washed with ethyl acetate (50 mL)
  8. washthe filtrate was washed with H2O (5 mL) and brine (5 mL)
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated to a brown oil

Sources & evidence

ORD record
ord-67b448db23e04747acf7f307f3fc1cf9
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

Loading…