Potassium Hydroxide → 2,6,7-trimethyl-1-(2-{[(2E)-3-phenylprop-2-enyl]oxy}ethyl)-1H-imidazo[4,5-c]pyridin-4-amine

HRID 1352552Notes

Reaction equation

HRID 1352552 reaction equation
[CH3:1][C:2]1[N:3]([CH2:20][CH2:21][O:22][CH2:23]/[CH:24]=[CH:25]/[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:4]2[C:9]([CH3:10])=[C:8]([CH3:11])[N:7]=[C:6](OC3C=CC=CC=3)[C:5]=2[N:19]=1.C([O-])(=O)C.[NH4+:36].[OH-].[K+]>>[CH3:1][C:2]1[N:3]([CH2:20][CH2:21][O:22][CH2:23]/[CH:24]=[CH:25]/[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:4]2[C:9]([CH3:10])=[C:8]([CH3:11])[N:7]=[C:6]([NH2:36])[C:5]=2[N:19]=1

Participants

4

Reactant 3

HCID 14797Potassium HydroxideHCID 517165Ammonium AcetateHCID 219129941-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl [(2E)-3-Phenylprop-2-enyl]Ether

Product 1

HCID 219133012,6,7-trimethyl-1-(2-{[(2E)-3-phenylprop-2-enyl]oxy}ethyl)-1H-imidazo[4,5-c]pyridin-4-amineYield 31.7%

Conditions

Temperature
150 °C

Procedure

1-[2,6,7-Trimethyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]eth-2-yl [(2E)-3-phenylprop-2-enyl]ether (2.9 g, 7.013 mmol) from Part A and ammonium acetate (54 g) were combined in a glass pressure vessel. The vessel was sealed with a teflon screw cap, and the reaction mixture was heated to 150° C. for 45 hours. The reaction was complete, and the resulting reaction solution was cooled with an ice bath, basified to a pH of about 13 with 1N potassium hydroxide, and washed with dichloromethane (4×500 mL). The combined organic portions were washed with water (3×) and brine (3×), dried with magnesium sulfate, filtered, and concentrated under reduced pressure to a white solid. The resulting white solid was slowly passed through a column containing 200 g silica that had been heated with 1% diethyl ether in dichloromethane using 98/2 dichloromethane/methanol. Two crops of product were isolated from the eluted solution, and both were recrystallized from isopropyl alcohol. The resulting white powder was dried under vacuum for 18 hours to provide 0.7479 g of 2,6,7-trimethyl-1-(2-{[(2E)-3-phenylprop-2-enyl]oxy}ethyl)-1H-imidazo[4,5-c]pyridin-4-amine, m.p. 143.7–144.8° C.

Workup

  1. customscrew cap
  2. customthe resulting reaction solution
  3. temperaturewas cooled with an ice bath
  4. washwashed with dichloromethane (4×500 mL)
  5. washThe combined organic portions were washed with water (3×) and brine (3×)
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure to a white solid
  9. additioncontaining 200 g silica that
  10. temperaturehad been heated with 1% diethyl ether in dichloromethane using 98/2 dichloromethane/methanol
  11. customTwo crops of product were isolated from the eluted solution
  12. customboth were recrystallized from isopropyl alcohol
  13. customThe resulting white powder was dried under vacuum for 18 hours

Sources & evidence

ORD record
ord-88f5bd813b634a208c3b75c343e5d3a6
Source dataset
uspto-grants-2007_05
Patent number
US07220758B2

Reaction notes

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