تفاعل #680133

ord-7a971cdceddc409383ea48dca7c951a6

المذيبات

ظروف التفاعل

درجة الحرارة
65°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىA 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. 2
    أخرىAfter three cycles of vacuum/argon flush
  3. 3
    درجة الحرارةAfter cooling to room temperature the reaction
  4. 4
    ترشيحwas filtered
  5. 5
    تركيزThe filtrate was concentrated under reduced pressure
  6. 6
    أخرىthe resulting residue was purified by silica-gel column chromatography
  7. 7
    غسيلeluting with dichloromethane/methanol (50:1 to 30:1)

الإجراء التجريبي

A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with (S)-5-bromo-1-methyl-3-(5-(2-methyl-4-(oxetan-3-yl) piperazin-1-yl)pyrazin-2-ylamino)pyridin-2(1H)-one 230f (200 mg, 0.46 mmol), {3-[(acetoxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]-dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (366 mg, 0.92 mmol), Pd(dppf)Cl2 (38 mg, 0.046 mmol), sodium acetate (126 mg, 0.92 mmol), K3PO4 (196 mg, 0.92 mmol), water (0.5 mL), and acetonitrile (10 mL). After three cycles of vacuum/argon flush, the mixture was heated at 65° C. for 3 hrs. After cooling to room temperature the reaction was filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (50:1 to 30:1) to afford 235a as brown solid (100 mg, 31%). MS-ESI: [M+H]+ 708.5.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US09238655B2uspto-grants-2016_01