Potassium Hydroxide → HCID 21913787, compound

HRID 1352541Notes

Reaction equation

HRID 1352541 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:23][CH2:24][O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9](OC3C=CC=CC=3)[C:8]=2[N:22]=1)[CH3:2].C([O-])(=O)C.[NH4+:37].[OH-].[K+]>>[CH2:26]([O:25][CH2:24][CH2:23][N:6]1[C:7]2[C:12]([CH3:13])=[C:11]([CH3:14])[N:10]=[C:9]([NH2:37])[C:8]=2[N:22]=[C:5]1[CH2:4][O:3][CH2:1][CH3:2])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 517165Ammonium AcetateHCID 21913918HCID 21913918, compound

Product 1

HCID 21913787HCID 21913787, compoundYield 40.2%

Conditions

Temperature
156 °C

Procedure

2-(Ethoxymethyl)-1-[2-(benzyloxy)ethyl]-6,7-dimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridine (4.33 g, 10.03 mmol) was placed in a glass reaction flask, and then ammonium acetate (45 g) was added. The flask was sealed with a teflon screw cap and heated to 156° C. for 44 hours. The reaction was determined to be complete by HPLC analysis, and the desired product's molecular weight was confirmed by LC/MS. The resulting solution was basified with 1 N potassium hydroxide to a pH of about 14. The basic solution was extracted with dichloromethane (5×), and the organic layers were combined, washed with water (3×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting oil was triturated with diethyl ether. After the resulting solids were filtered off and dried, they were recrystallized from ethyl acetate/diethyl ether and again dried. NMR analysis or the recrystallized solids indicated impurities. The recrystallized solids were dissolved in ethanol. Hydrochloric acid (10 mL, 1 N) was added to the ethanol solution, and the resulting salt was filtered off and dissolved in water. The resulting aqueous solution was basified with 1 N potassium hydroxide to a pH of about 14 and extracted with dichloromethane (4×). The organic layers were combined, washed with water (2×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a white solid. The white solid was dried to provide 1.4285 g of 1-[2-(benzyloxy)ethyl]-2-(ethoxymethyl)-6,7-dimethyl-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 107.3–108.2° C.

Workup

  1. customscrew cap
  2. extractionThe basic solution was extracted with dichloromethane (5×)
  3. washwashed with water (3×) and brine (3×)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oil was triturated with diethyl ether
  8. filtrationAfter the resulting solids were filtered off
  9. customdried
  10. customthey were recrystallized from ethyl acetate/diethyl ether
  11. customagain dried
  12. dissolutionThe recrystallized solids were dissolved in ethanol
  13. additionHydrochloric acid (10 mL, 1 N) was added to the ethanol solution
  14. filtrationthe resulting salt was filtered off
  15. dissolutiondissolved in water
  16. extractionextracted with dichloromethane (4×)
  17. washwashed with water (2×) and brine (3×)
  18. dry with materialdried with magnesium sulfate
  19. filtrationfiltered
  20. concentrationconcentrated under reduced pressure to a white solid
  21. customThe white solid was dried

Sources & evidence

ORD record
ord-d2f898a2aefa4acdb96635608cac1331
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

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