Cesium carbonate → N-(3-Fluoro-4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

HRID 347483ノート

反応式

HRID 347483 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].Cl[C:24]1[C:25]2[S:32][CH:31]=[CH:30][C:26]=2[N:27]=[CH:28][N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>[Cu]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:24]1[C:25]2[S:32][CH:31]=[CH:30][C:26]=2[N:27]=[CH:28][N:29]=1

参加物

6

反応物 4

HCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 27358214-Chlorothieno[3,2-d]pyrimidineHCID 44203043N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide

生成物 1

HCID 58798989N-(3-Fluoro-4-(thieno[3,2-d]pyrimidin-4-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

試薬・触媒・溶媒 1

HCID 62652Cuprous chloride触媒

反応条件

温度
120 °C

実験手順

N1-(3-Fluoro-4-hydroxyphenyl)-N3-(4-fluorophenyl)malonamide (46 mg, 0.15 mmol), 4-chlorothieno[3,2-d]pyrimidine (17 mg, 0.10 mmol), cesium carbonate (49 mg, 0.15 mmol), and copper(I) chloride (10 mg, 0.10 mmol) were placed in a test tube. The tube was sealed, flushed with nitrogen, charged with 1-methyl-2-pyrrolidinone (0.3 mL) followed by 2,2,6,6-tetramethyl-3,5-heptanedione (4.0 μL, 0.02 mmol). The reaction was stirred at 120° C. for 2 h. The reaction mixture was purified by preparative 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 to give the desired product as a colorless oil. Lyophilization with methanol/water gave the title compound (23 mg, 52%) as a white solid. 1H NMR (CD3OD) δ 8.54 (s, 1H), 8.21 (d, 1H, J=5.5 Hz), 7.69 (dd, 1H, J=12.4, 2.0 Hz), 7.49 (m, 3H), 7.27 (m, 2H), 6.96 (t, 2H, J=8.9 Hz), 3.47 (s, 2H); MS(ESI+) m/z 441.1 (M+H)+.

後処理

  1. customThe tube was sealed
  2. customflushed with nitrogen
  3. additioncharged with 1-methyl-2-pyrrolidinone (0.3 mL)
  4. customThe reaction mixture was purified by preparative 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

出典と根拠

ORDレコード
ord-e792699e89564602b48616563ee5c5e5
出典データセット
uspto-grants-2007_02
特許番号
US07173031B2

反応ノート

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