تفاعل #70196

ord-e6009ce13687449ebf31cfe81f1476e0

ظروف التفاعل

درجة الحرارة
0°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.ADDITIONIn a 100 mL addition funnel
  2. 2
    درجة الحرارةwhile maintaining the temperature at 0° C
  3. 3
    درجة الحرارةto warm to ambient temperature as it
  4. 4
    أخرىthe reaction
  5. 5
    workup.STIRRINGAfter stirring the precipitate
  6. 6
    ترشيحwas filtered
  7. 7
    أخرىdried

الإجراء التجريبي

In a dry flask charged with a 1:1 mixture of dichloromethane-dimethylformamide (100 ml) was placed 1-(2-{2-Cyclohexyl-2-[(pyrazine-2-carbonyl)-amino]-acetylamino}-3,3-dimethyl-butyryl)-octahydro-indole-2-carboxylic acid 32a (2.0 g, 4.28 mmols), PyBOP (2.5 g, 4.7 mmol), and N-methyl-morpholine (2.4 ml, 21.4 mmol) and the reaction placed under an atmosphere of nitrogen. In a 100 mL addition funnel was placed a solution of the amine 14(1.0 g, 4.7 mmols) and N-methyl-morpholine (0.60 ml, 5.35 mmol) in a 1:1 mixture of dichloromethane-dimethylformamide (10 ml). The reaction was cooled to 0° C., and the amine was added while maintaining the temperature at 0° C. The reaction was allowed to warm to ambient temperature as it was stirred over night. HPLC analysis showed the reaction to be complete, and then the reaction was diluted with water to 500 mL. After stirring the precipitate was filtered and dried to give 2.4 g (82% yield) of 32 as a beige solid. This material was used as is in the next step without further purification. HPLC: RT=5.66 min, (10-90% acetonitrile-water over 7 minutes); LC/MS: retention time 3.94 min (10-90% acetonitrile-water over 5 minutes); M+H+=685.5.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08536136B2uspto-grants-2013_09