Dichloromethane → HCID 67575630, compound

HRID 343181Notes

Reaction equation

HRID 343181 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[NH:5][C:4](=[O:28])[CH2:3]1.C([O-])(=O)C.[K+].Br[C:35]1[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=1.ClCCl>CS(C)=O>[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:35]2[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=2)[C:4](=[O:28])[CH2:3]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 142684-BromopyridineHCID 517044Potassium AcetateHCID 54046412HCID 54046412, compound

Product 1

HCID 67575630HCID 67575630, compoundYield 50.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirring solution of 700 mg (1.89 mmol) 2-(2,4-Dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide in DMSO is added 370 mg of Cu powder (5.8 mmol, 3 equiv), 380 mg of potassium acetate (3.88 mmol, 2 equiv) and 500 mg of 4-bromopyridine (3.16 mmol, 1.7 equiv, freshly free-based from the hydrochloride salt). The reaction is heated to 100° C. for 16 h then poured onto ice. Dichloromethane is added, and the mixture is filtered through celite. The filtrate is poured into a separatory funnel containing 100 mL of H2O, and the layers separated. 2 mL of a 30% solution of NH4OH were added to the aqueous layer, and the resulting blue solution is extracted with dichloromethane. The combined organics were dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel flash column chromatography to afford 437 mg of 2-(2,4-Dioxo-5-pyridin-4-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide as a white solid: mp. 211°-213° C.; 1H NMR (CDCl3, 400 MHz) δ8.61 (d, br, 2H, J=5.4), 7.43 (d, 1H, J=8.1), 7.36-7.14 (m, 5H), 6.99-6.22 (m, 4H), 5.03 (m, 1H), 4.26 (dd, br, 2H, J=16.6, 28.5), 3.87 (s, 3H), 3.55 (dd, 2H, J=12.0, 36.4), 1.09 (d, 6H, J=6.8); low resolution MS (FAB)m/e 459 (MH+).

Workup

  1. additionthen poured onto ice
  2. filtrationthe mixture is filtered through celite
  3. additionThe filtrate is poured into a separatory funnel
  4. additioncontaining 100 mL of H2O
  5. customthe layers separated
  6. addition2 mL of a 30% solution of NH4OH were added to the aqueous layer
  7. extractionthe resulting blue solution is extracted with dichloromethane
  8. dry with materialThe combined organics were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue is purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-ff222f58d0e2400294a5e15020bcd4c8
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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