تفاعل #563206

ord-46e3d813ceef4f8e8be785cef45bbcdf

المذيبات

ظروف التفاعل

درجة الحرارة
100°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةAfter cooling to room temperature
  2. 2
    أخرىThe reaction mixture was irradiated (microwave) at 120° C. for 2 h
  3. 3
    درجة الحرارةThe reaction mixture was cooled
  4. 4
    درجة الحرارةcooled to room temperature
  5. 5
    ترشيحfiltered through Na2SO4
  6. 6
    أخرىThe contents were purified directly by silica gel chromatography (eluent: 5% MeOH/CH2Cl2)

الإجراء التجريبي

6-Bromo-3,4-dihydro-1,8-naphthyridin-2(1H)-one (200 mg, 0.881 mmol) (J. Med. Chem. 2003; 46; 9; 1627-1635), bis(pinacolato)diboron (268 mg, 1.057 mmol), Pd(dppf) (35.7 mg, 0.044 mmol) and potassium acetate (259 mg, 2.64 mmol) were suspended in 1,4-Dioxane (8 mL), and stirred with heating at 100° C. for 1 h. After cooling to room temperature, 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (329 mg, 0.881 mmol), bis(triphenylphosphine)palladium(II) chloride (71.9 mg, 0.088 mmol) and sodium bicarbonate (222 mg, 2.64 mmol) were added, followed by DME (5 mL) and water (3 mL). The reaction mixture was irradiated (microwave) at 120° C. for 2 h. The reaction mixture was cooled cooled to room temperature and filtered through Na2SO4. The contents were purified directly by silica gel chromatography (eluent: 5% MeOH/CH2Cl2) to furnish the desired product as a grey solid after evaporation and precipitation from warm EtOAc/MeOH (1:9). The product was collected as 55 mg (13%). LCMS E-S (M+H)=486.3 1H NMR (400 MHz, DMSO-d6) δ ppm 11.57 (br. s., 1H), 10.74 (s, 1H), 8.99 (d, J=2.27 Hz, 1H), 8.93 (t, J=4.93 Hz, 1H), 8.44 (d, J=1.77 Hz, 1H), 8.37 (s, 1H), 8.16 (s, 1H), 5.91 (s, 1H), 5.29-5.40 (m, 1H), 4.42 (d, J=5.05 Hz, 2H), 3.04 (t, J=7.58 Hz, 2H), 2.53-2.62 (m, 2H), 2.23 (s, 3H), 2.13 (s, 3H), 1.54 (d, 6H).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08637509B2uspto-grants-2014_01