N,N'-Dimethylethylenediamine → (R)-3-(6-Ethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

HRID 533918ノート

反応式

HRID 533918 の反応式
[CH2:1]([O:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C@@H:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])=[CH:6][CH:5]=1)[CH3:2].Br[C:18]1[CH:26]=[C:25]2[C:21]([CH2:22][CH2:23][C:24]2=[O:27])=[C:20]([F:28])[CH:19]=1.CNCCNC>O1CCOCC1>[CH2:1]([O:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C@@H:11]2[CH2:15][CH2:14][N:13]([C:18]3[CH:26]=[C:25]4[C:21](=[C:20]([F:28])[CH:19]=3)[CH2:22][CH2:23][C:24]4=[O:27])[C:12]2=[O:16])=[CH:6][CH:5]=1)[CH3:2]

参加物

5

反応物 3

HCID 8070N,N'-DimethylethylenediamineHCID 509894266-Bromo-4-fluoro-2,3-dihydro-1H-inden-1-oneHCID 86715109(R)-3-((6-ethoxypyridin-3-yl)oxy)pyrrolidin-2-one

生成物 1

HCID 74767655(R)-3-(6-Ethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

In a further alternative preparation a mixture of (R)-3-((6-ethoxypyridin-3-yl)oxy)pyrrolidin-2-one (2.00 g), 6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one (2.30 g), N,N′-dimethyl-ethylene-diamine (10 mL) and 1,4-dioxane (20 mL) was purged with argon and cesium carbonate (3.8 g) and copper(I) iodide (100 mg) were added. The mixture was heated to 100° C. for 1.5 hours. After cooling to r.t. the mixture was diluted with EA and washed with water (5 times) and brine. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by SGC (eluent: heptane with 0 to 70% EA) to provide Example 2-08. 1H-NMR (400 MHz, DMSO) δ 7.99 (1H, dd, J=11.3, 1.8 Hz), 7.97 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=8.9, 3.1 Hz), 6.76 (1H, d, J=8.9 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.24 (2H, q, J=7.0 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.11 (2H, m), 2.72 (2H, m), 2.69 (1H, m), 2.13 (1H, m), 1.30 (3H, t, J=7.0 Hz).

後処理

  1. customIn a further alternative preparation
  2. customwas purged with argon and cesium carbonate (3.8 g) and copper(I) iodide (100 mg)
  3. additionwere added
  4. temperatureAfter cooling to r.t. the mixture
  5. additionwas diluted with EA
  6. washwashed with water (5 times) and brine
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by SGC (eluent: heptane with 0 to 70% EA)
  10. customto provide Example 2-08

出典と根拠

ORDレコード
ord-2036a86608ae4642b1b2fc0f28be29f2
出典データセット
uspto-grants-2014_10
特許番号
US08853412B2

反応ノート

読み込み中…