تفاعل #332022

ord-fd2cd8463e294ccd9849cc724f8d443d

معادلة التفاعل

CC#N
acetonitrile
CCN(CC)CC
triethylamine
C=CC(=O)N(C)C
N,N-dimethylacrylamide
COCCc1nc2cnc3ccc(Br)cc3c2n1CCCN1CCCC1=O
1-{3-[8-bromo-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-one
COCCc1nc2cnc3ccc(C=CC(=O)N(C)C)cc3c2n1CCCN1CCCC1=O
3-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylprop-2-enamide
المردود 86.4%

المذيبات

ظروف التفاعل

درجة الحرارة
120°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىA thick walled glass tube, equipped with a stir bar
  2. 2
    أخرىThe reaction mixture was purged with nitrogen
  3. 3
    أخرىthe tube was sealed
  4. 4
    درجة الحرارةThe reaction was maintained at 120° C. for 18 hours
  5. 5
    درجة الحرارةcooled to ambient temperature
  6. 6
    درجة الحرارةUpon cooling a precipitate
  7. 7
    أخرىformed
  8. 8
    أخرىThe remaining insoluble material was removed by filtration through a 0.2 micron PTFE membrane
  9. 9
    ترشيحfilter
  10. 10
    تركيزThe filtrate was concentrated under reduced pressure
  11. 11
    أخرىpurified by chromatography
  12. 12
    غسيلeluting with a 0-7% gradient of methanol in dichloromethane)

الإجراء التجريبي

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (8 mg, 0.04 mmol), acetonitrile (50 mL), triethylamine (0.9 mL, 5.22 mmol), tri-o-tolylphosphine (30 mg, 0.10 mmol), N,N-dimethylacrylamide (189 mg, 1.91 mmol) and 1-{3-[8-bromo-2-(2-methoxyethyl)-1H-imidazo[4,5-c]quinolin-1-yl]propyl}pyrrolidin-2-one (0.75 g, 1.7 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated at 120° C. in an oil bath. The reaction was maintained at 120° C. for 18 hours and then cooled to ambient temperature. Upon cooling a precipitate formed that was dissolved by the addition of methanol and chloroform. The remaining insoluble material was removed by filtration through a 0.2 micron PTFE membrane filter. The filtrate was concentrated under reduced pressure and purified by chromatography using a HORIZON HPFC system (silica cartridge, eluting with a 0-7% gradient of methanol in dichloromethane) to provide 660 mg of 3-{2-(2-methoxyethyl)-1-[3-(2-oxopyrrolidin-1-yl)propyl]-1H-imidazo[4,5-c]quinolin-8-yl}-N,N-dimethylprop-2-enamide as an off-white solid.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08658666B2uspto-grants-2014_02