تفاعل #332018

ord-169d0131231f450585d2a0ac379d145f

معادلة التفاعل

CCN(CC)CC
triethylamine
Cc1ccccc1P(c1ccccc1C)c1ccccc1C
tri-o-tolylphosphine
C=CC(=O)N(C)C
N,N-dimethylacrylamide
CCc1nc2cnc3cc(Br)ccc3c2n1CC(C)(C)O
1-(7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol
CCc1nc2cnc3cc(C=CC(=O)N(C)C)ccc3c2n1CC(C)(C)O
3-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide
المردود 86.9%

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 0-25% gradient of CMA in chloroform)
  13. 13
    غسيلThe resulting product was washed with 1% aqueous sodium carbonate
  14. 14
    ترشيحfiltered

الإجراء التجريبي

A thick walled glass tube, equipped with a stir bar, was charged with palladium (II) acetate (50 mg, 0.22 mmol), acetonitrile (50 mL), triethylamine (1.80 mL, 13.0 mmol), tri-o-tolylphosphine (200 mg, 0.65 mmol), N,N-dimethylacrylamide (511 mg, 5.16 mmol) and 1-(7-bromo-2-ethyl-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol (1.50 g, 4.30 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, eluting with a 0-25% gradient of CMA in chloroform). The resulting product was washed with 1% aqueous sodium carbonate and filtered to provide 1.37 g of 3-[2-ethyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]-N,N-dimethylprop-2-enamide as an off-white solid, mp 196-198° C.

المصدر

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