تفاعل #45141

ord-04ef702d9aa349aa9a295d641b6c2474

المذيبات

ظروف التفاعل

درجة الحرارة
60°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةThe reaction mixture was cooled
  2. 2
    أخرىquenched with methanol (15 ml) and 2N hydrochloric acid (5 ml)
  3. 3
    أخرىThe crude reaction mixture
  4. 4
    أخرىwas purified by ion exchange chromatography on a SCX column
  5. 5
    غسيلeluting with 7N ammonia in methanol
  6. 6
    أخرىThe appropriate fractions were evaporated
  7. 7
    أخرىto give an oil
  8. 8
    أخرىThe crude product was purified by silica column chromatography
  9. 9
    غسيلeluting with a gradient of 0 to 10% 2.5N ammonia/MeOH in DCM
  10. 10
    أخرىPure fractions were evaporated to dryness
  11. 11
    أخرىto afford, on crystallisation from DCM/diethyl ether

الإجراء التجريبي

A 2M solution of trimethylaluminium (2.500 mL, 5.00 mmol) in toluene, was added dropwise to a stirred suspension of ethyl 4-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)benzoate (0.643 g, 2 mmol) and 5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-amine (0.495 g, 2.00 mmol) in toluene (10 mL) at room temperature. The solution was then heated at 60° C. for 18 h. The reaction mixture was cooled and quenched with methanol (15 ml) and 2N hydrochloric acid (5 ml). The crude reaction mixture was purified by ion exchange chromatography on a SCX column, eluting with 7N ammonia in methanol. The appropriate fractions were evaporated to give an oil. The crude product was purified by silica column chromatography, eluting with a gradient of 0 to 10% 2.5N ammonia/MeOH in DCM. Pure fractions were evaporated to dryness to afford, on crystallisation from DCM/diethyl ether, the title compound (0.322 g, 33.7%) as a cream solid.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07737149B2uspto-grants-2010_06