Dimethylformamide → ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

HRID 2235928ノート

反応式

HRID 2235928 の反応式
[Br:1][C:2]1[CH:3]=[N:4][C:5]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)=[N:6][CH:7]=1.[H-].[Na+].[NH4+].[Cl-].[CH3:32]N(C=O)C>>[Br:1][C:2]1[CH:7]=[N:6][C:5]([N:8]([CH3:32])[CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[C@H:18]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:17][CH2:16]3)=[N:4][CH:3]=1

参加物

5

反応物 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59300487ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate

生成物 1

HCID 59300480ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)(methyl)amino]propoxy}-2,3-dihydro-1H-inden-1-yl)acetate収率 21%

実験手順

To a solution of ethyl ((1S)-5-{3-[(5-bromo-2-pyrimidinyl)amino]propoxy}2,3-dihydro-1H-inden-1-yl)acetate (Example 281, 500 mg, 1.15 mmol) in DMF (10 mL) was added NaH [H2 evolution], followed by Mel (180 mg, 1.27 mmol) added over 5 min. The reaction mixture was stirred at rt for 4 h, NH4Cl (10% aqueous solution) was added, after which the mixture was concentrated under reduced pressure. The residue was taken up in EtOAc, then washed with water and brine successively. The organic phase was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to provide the product (600 mg, 21%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 1.29 (t, 3H), 1.71-1.81 (m, 1H), 2.05-2.13 (m, 2H), 2.34-2.45 (m, 2H), 2.73 (dd, 1H), 2.73-2.94 (m, 2H), 3.14 (s, 3H), 3.49-3.56 (m, 1H), 3.77 (t, 2H), 3.97 (t, 2H), 4.18 (q, 2H), 6.74 (dd, 1H), 6.75 (d, 1H), 7.05 (d, 1H), 8.24 (s, 2H).

後処理

  1. additionadded over 5 min
  2. concentrationafter which the mixture was concentrated under reduced pressure
  3. washwashed with water and brine successively
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-6eb45af4366a48938f3548f63b96be6b
出典データセット
uspto-grants-2010_05
特許番号
US07714004B2

反応ノート

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