3-Bromopyridine → 2-(2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro benzo[b][1.4]diazepin-1-yl)-N-isopropyl-N-phenylacetamide

HRID 343118Notes

Reaction equation

HRID 343118 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:19]([CH3:21])[CH3:20])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[NH:5][C:4](=[O:26])[CH2:3]1.Br[C:28]1[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=1.C([O-])(=O)C.[K+]>CN(C=O)C.CCOC(C)=O.[Cu]>[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:19]([CH3:21])[CH3:20])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:22]=[CH:23][CH:24]=[CH:25][C:6]=2[N:5]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:4](=[O:26])[CH2:3]1

Participants

7

Reactant 3

HCID 122863-BromopyridineHCID 517044Potassium AcetateHCID 867535892-(2,4-Dioxo-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide

Product 1

HCID 676962912-(2,4-dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro benzo[b][1.4]diazepin-1-yl)-N-isopropyl-N-phenylacetamideYield 64.9%

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
125 °C

Procedure

To a stirring solution of 3.3 g (9.39 mmol) of 2-(2,4-Dioxo-2,3,4,5-tetrahydro benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl acetamide, prepared as in Intermediate 47, in 25 mL of DMF is added 2.97 g (18.78 mmol, 2 equiv.) of 3-bromopyridine, 1.84 g (18.78 mmol, 2 equiv.) of potassium acetate, and 1.19 g (18.78 mmol, 2 equiv.) of copper powder. The suspension is heated to 125° C. for 8 h and then cooled to RT. It is diluted with 500 mL EtOAc and filtered through a bed of celite. The filtrate is washed with H2O (2×500 mL), conc. NH4OH (2×350 mL) and then dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash column chromatography using hexane/EtOAc 1/1 as eluent afforded 2.61 g of the title compound as an oil: 1H NMR (CDCl3, 300 MHz) δ8.50 (m, 1H), 7.78 (d, 1H, J=9), 7.48-7.25 (m, 7H), 7.14 (t, 1H, J=8), 6.88 (d, 1H, J=10), 5.06-4.95 (m, 1H), 4.30-4.09 (m, 3H), 3.54 (q, 1H, J=13, 6), 1.7 (s, 1H), 1.42 (d, 2H, J=6), 1.10 (dd, 6H, J=9,2).

Workup

  1. temperaturecooled to RT
  2. filtrationfiltered through a bed of celite
  3. washThe filtrate is washed with H2O (2×500 mL), conc. NH4OH (2×350 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvents removed in vacuo
  6. customPurification by silica gel flash column chromatography

Sources & evidence

ORD record
ord-7367ac4342474c78beb5c416b4b316dd
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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