Pyridine → N1-(3-Fluoro-4-(pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

HRID 2237185ノート

反応式

HRID 2237185 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:22])[CH2:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[OH:8].[N:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.N1C=CC=CC=1>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:22])[CH2:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][C:26]1[CH:27]=[CH:28][N:23]=[CH:24][CH:25]=1

参加物

6

反応物 3

HCID 1049PyridineHCID 2734379(Pyridin-4-yl)boronic acidHCID 44203043N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide

生成物 1

HCID 59852940N1-(3-Fluoro-4-(pyridin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide収率 21%

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

反応条件

温度
120 °C

実験手順

N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide (31 mg, 0.10 mmol), copper(II) acetate (27 mg, 0.15 mmol), pyridin-4-ylboronic acid (25 mg, 0.20 mmol), and pyridine (16 μL, 0.20 mmol) were placed in a pressure tube in that order. The tube was charged with methylene chloride (0.5 mL) and sealed. The reaction was stirred at 120° C. for 5 h. The reaction mixture was filtered through silica gel using 5% methanol/ethyl acetate. After concentration, the crude product was purified by prep HPLC. The appropriate fraction was concentrated to remove methanol and the resulting aqueous solution was made basic with saturated NaHCO3 solution (5 mL). The aqueous solution was extracted with EtOAc (3×10 mL) and the combined organic extracts were dried over anhydrous Na2SO4 and concentrated in vacuo. The product was treated with 4N HCl in dioxane and concentrated. Lyophilization with water gave the title compound (8 mg, 21%) as a yellow solid. 1H NMR (CD3OD) δ 8.31 (d, 2H, J=6.1 Hz), 7.72 (dd, 1H, J=12.7, 2.4 Hz), 7.49-7.46 (m, 2H), 7.27-7.25 (m, 1H), 7.15 (t, 1H, J=8.8 Hz), 6.97 (t, 2H, J=8.7 Hz), 6.85 (dd, 2H, J=5.1, 1.2 Hz), 3.46 (s, 2H); MS(ESI+) m/z 384.21 (M+H)+.

後処理

  1. customsealed
  2. filtrationThe reaction mixture was filtered through silica gel using 5% methanol/ethyl acetate
  3. concentrationAfter concentration
  4. customthe crude product was purified by prep HPLC
  5. concentrationThe appropriate fraction was concentrated
  6. customto remove methanol
  7. extractionThe aqueous solution was extracted with EtOAc (3×10 mL)
  8. dry with materialthe combined organic extracts were dried over anhydrous Na2SO4
  9. concentrationconcentrated in vacuo
  10. additionThe product was treated with 4N HCl in dioxane
  11. concentrationconcentrated

出典と根拠

ORDレコード
ord-2bd6740570ee4d8cb3b2c688566f2f76
出典データセット
uspto-grants-2010_05
特許番号
US07714138B2

反応ノート

読み込み中…