Ammonia → 2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine

HRID 606107Notes

Reaction equation

HRID 606107 reaction equation
Cl[C:2]1[C:11]2[N:12]=[C:13]([CH2:28][CH3:29])[N:14]([CH2:15][C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH:17]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH3:30]>CO.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:28]([C:13]1[N:14]([CH2:15][C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH:17]=2)[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:30])[C:11]=2[N:12]=1)[CH3:29]

Participants

6

Reactant 2

HCID 222AmmoniaHCID 866168914-chloro-2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinoline

Product 1

HCID 590266992-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

4-Chloro-2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinoline (2.624 g, 6.451 mmol), 7 N ammonia in methanol (40 mL), and tetrakis(triphenylphosphine)palladium(0) were combined in a pressure vessel and heated at 120° C. for 16 hours. An analysis by HPLC indicated that the reaction was incomplete. The volatiles were removed under reduced pressure, and the residue was dissolved in chloroform. The solution was washed sequentially with aqueous potassium carbonate, water, and brine; dried over magnesium sulfate; filtered; and concentrated under reduced pressure. The resulting dark yellow solid was added to a pressure vessel with 7 N ammonia in methanol (60 mL), and the reaction was sealed and heated at 150° C. for 18 hours. The volatiles were removed under reduced pressure, and the residue was stirred with 0.5 N potassium hydroxide in methanol for 30 minutes. The resulting solid was isolated by filtration, diluted with dichloromethane, purified by column chromatography on silica gel (eluting with 5% to 10% CMA in chloroform), triturated with diethyl ether and filtered, and recrystallized from acetonitrile after a hot filtration. The crystals were isolated by filtration, washed with diethyl ether, and dried to provide 0.139 g of 2-ethyl-1-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-1H-imidazo[4,5-c]quinolin-4-amine as a white powder, mp 232.0-233.0° C.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. dissolutionthe residue was dissolved in chloroform
  3. washThe solution was washed sequentially with aqueous potassium carbonate, water, and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationand concentrated under reduced pressure
  7. additionThe resulting dark yellow solid was added to a pressure vessel with 7 N ammonia in methanol (60 mL)
  8. customthe reaction was sealed
  9. temperatureheated at 150° C. for 18 hours
  10. customThe volatiles were removed under reduced pressure
  11. customThe resulting solid was isolated by filtration
  12. custompurified by column chromatography on silica gel (eluting with 5% to 10% CMA in chloroform)
  13. customtriturated with diethyl ether
  14. filtrationfiltered
  15. customrecrystallized from acetonitrile
  16. filtrationafter a hot filtration
  17. customThe crystals were isolated by filtration
  18. washwashed with diethyl ether
  19. customdried

Sources & evidence

ORD record
ord-2da3fbb68e954a3ca987f5c6a4c71555
Source dataset
uspto-grants-2011_03
Patent number
US07915281B2

Reaction notes

Loading…