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

HRID 533918노트

반응식

HRID 533918 반응식
[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]

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-2036a86608ae4642b1b2fc0f28be29f2
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853412B2

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