3-Bromopyridine → HCID 67611178, compound

HRID 343117Notes

Reaction equation

HRID 343117 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:36]=[N:37][CH:38]=[CH:39][CH:40]=1>CN(C=O)C>[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:36]=[N:37][CH:38]=[CH:39][CH:40]=2)[C:4](=[O:28])[CH2:3]1

Participants

5

Reactant 3

HCID 122863-Bromopyridine2×HCID 517044Potassium Acetate3×HCID 54046412HCID 54046412, compound

Product 1

HCID 67611178HCID 67611178, compoundYield 49.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a stirring solution of 26.6 g (69.7 mmol) 2-(2,4-Dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 46, in 1 L DMF is added 13.3 g (209 mmol, 3 equiv) of Cu powder, 13.7 g (139 mmol, 2 equiv) of potassium acetate and 13.4 mL (139 mmol, 2 equiv) of 3-bromopyridine. The reaction is heated to 120° C. After 5 h, an additional 13 g (133 mmol) of potassium acetate and 15 mL (156 mmol) of 3-bromopyridine were added, and the reaction is allowed to stir overnight. After ca. 18 h, an additional 15 g (236 mmol) Cu and 5 g (51 mmol) potassium acetate were added, and stirring is continued for an additional 24 h. The reaction is then allowed to cool, and is filtered through celite, rinsing with ethyl acetate. The organics were extracted with 10% NH4OH, the twice with water. The aqueous layer is extracted with EtOAc/ethyl ether. The combined organics were dried (MgSO4) filtered and concentrated in vacuo to afford an oil. This is purified by silica gel flash chromatography to afford 15.8 g of the title compound as a white powder as well as 1.5 g of recovered unreacted starting material: 1H NMR (CDCl3, 400 MHz) δ8.68 (s, br, 2H), 7.86 (d, 1H, J=7.8), 7.36 (d, 2H, J=7.6) 7.27-7.10 (m, 6H ) 6.95 (t, 2H, J=7.6) 6.84 (d, 1H, J=7.1) 4.95 (m, 1H), 4.23 (s, br, 2H) 3.82 (s, 3H) 3.53 (dd, 2H, J=12.2, 44) 1.04 (dd, 6H, J=2.4, 6.8); low resolution MS (FAB)m/e (MH+).

Workup

  1. waitAfter ca. 18 h
  2. stirringstirring
  3. waitis continued for an additional 24 h
  4. temperatureto cool
  5. filtrationis filtered through celite
  6. washrinsing with ethyl acetate
  7. extractionThe organics were extracted with 10% NH4OH
  8. extractionThe aqueous layer is extracted with EtOAc/ethyl ether
  9. dry with materialThe combined organics were dried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto afford an oil
  13. customThis is purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-42d4c02b9fab4e53aaf662c8cf9ead49
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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