Potassium Carbonate → HCID 19955587, compound

HRID 1779436Notes

Reaction equation

HRID 1779436 reaction equation
[CH2:1]([C:3]1[NH:13][C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[N:4]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]2[C:35](=[O:43])[C:36](=[O:42])[C:37]=2[O:38][CH:39]([CH3:41])[CH3:40])=[CH:24][CH:23]=1>CN(C)C=O>[CH2:1]([C:3]1[N:13]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]3[C:35](=[O:43])[C:36](=[O:42])[C:37]=3[O:38][CH:39]([CH3:41])[CH3:40])=[CH:26][CH:27]=2)[C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[N:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 19955579HCID 19955579, compoundHCID 178437439HCID 178437439, compound2×

Product 1

HCID 19955587HCID 19955587, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (0.66 g; preparable as described in Mantio et al, J. Med. Chem. 34, (1991), pp 2919/2922 and in EP-A-0400914; Merck), and anhydrous potassium carbonate (1.02 g) were added to a solution of 3-(4'-bromomethylbiphenyl-2-yl)-4-isopropoxycyclobut-3-ene-1,2-dione (1.88 g; preparable as described in Example 1(c)) in dry dimethylformamide (10 ml) and the resulting mixture was stirred at ambient temperature for approximately 16 hours. More 2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridine (0.33 g) was added to the dark reaction solution obtained, and stirring was continued at ambient temperature for an additional 24 hours. The resulting dark mixture was partitioned between ethyl acetate (100 ml) and water (50 ml). The organic layer was then separated, washed with water (50 ml), and dried over magnesium sulphate. The resulting solution was evaporated to leave a dark oil which was purified by flash chromatography on silica gel (eluting with 1% industrial methylated spirit in dichloromethane) followed by flash chromatography on silica gel (eluting with ethyl acetate) and flash chromatography on silica gel (eluting with 0% rising to 2% methanol in dichloromethane) to give 3-[4'-(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyrid-3-ylmethyl)biphenyl -2-yl]-4-isopropoxycyclobut-3-ene-1,2-dione, an active compound of the present invention, as a yellow foam (0.176 g) which melted slowly at 60° C. or above.

Workup

  1. customobtained
  2. stirringstirring
  3. waitwas continued at ambient temperature for an additional 24 hours
  4. customThe resulting dark mixture was partitioned between ethyl acetate (100 ml) and water (50 ml)
  5. customThe organic layer was then separated
  6. washwashed with water (50 ml)
  7. dry with materialdried over magnesium sulphate
  8. customThe resulting solution was evaporated
  9. customto leave a dark oil which
  10. customwas purified by flash chromatography on silica gel (eluting with 1% industrial methylated spirit in dichloromethane)

Sources & evidence

ORD record
ord-faccbc159c2b470a991c7395024027e1
Source dataset
uspto-grants-1997_05
Patent number
US05627191

Reaction notes

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