反応 #1955497

ord-eb76aa1ee183424d8d848e9d323237bc

溶媒

反応条件

温度
100°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度The reaction mixture was then heated at 100° C. under nitrogen until completion of the reaction (approx. 1 h)
  2. 2
    温度cooled to room temperature
  3. 3
    濃縮concentrated in vacuo to approx. half volume
  4. 4
    workup.ADDITIONThe mixture was diluted with water (20 mL)

実験手順

A mixture of 3-(4-bromo-thiophen-2-yl)-acrylonitrile 76 (0.33 g, 1.55 mmol), potassium acatete (0.47 g, 4.74 mmol), bis(pinacolato)diboron (0.84 g, 3.3 mmol), Pd(PPh3)4 (0.12 g, 0.1 mmol), and DMF (11 mL) was heated at 100° C. under nitrogen for 1 h. 4-Amino-2-bromo-thieno[3,2-c]pyridine-7-carboxylic acid amide 17 (0.28 g, 1.0 mmol), 2 M aqueous Na2CO3 solution (3.6 mL), and Pd(PPh3)4 (0.12 g, 0.11 mmol) were added. The reaction mixture was then heated at 100° C. under nitrogen until completion of the reaction (approx. 1 h), cooled to room temperature and concentrated in vacuo to approx. half volume. The mixture was diluted with water (20 mL) and the precipitate of 77 that formed was collected by filtration, washed with MeOH, and dried. 4-amino-2-[5-(cyano-vinyl)-thiophen-3-yl]-thieno[3,2-c]pyridine-7-carboxylic acid amide 77 was then dissolved in pyridine (5 mL) and EtOH (1 mL). To the resulting solution was added NaBH4 (0.16 g, 4.1 mmol). The solution was then heated at 100° C. until completion of the reaction (approx. 2 h) and then concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: 80% of CH2Cl2:MeOH:NH4OH (89:9:1) in CH2Cl2). The major fractions were combined and concentrated to give 78 (0.12 g) as a pale-yellow solid. 1H NMR (400 MHz, d6-DMSO) δ: 8.48 (s, 1H), 7.90 (br.s, 1H), 7.86 (s, 1H), 7.65 (d, J=1.4 Hz, 1H), 7.31 (s, 1H), 7.26 (br s, 1H), 7.12 (s, 2H), 3.17 (t, 2H), 2.92 (t, 2H). MS (EI) m/z (M+H+) 329 and (M+Na+) 351.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US07635695B2uspto-grants-2009_12