6-Bromo-4-fluoro-2,3-dihydro-1H-inden-1-one → (R)-3-(6-Cyclopropylmethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

HRID 533891노트

반응식

HRID 533891 반응식
[CH2:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C@@H:13]2[CH2:17][CH2:16][NH:15][C:14]2=[O:18])=[CH:8][CH:7]=1.Br[C:20]1[CH:28]=[C:27]2[C:23]([CH2:24][CH2:25][C:26]2=[O:29])=[C:22]([F:30])[CH:21]=1>O1CCOCC1>[CH:2]1([CH2:4][O:5][C:6]2[N:11]=[CH:10][C:9]([O:12][C@@H:13]3[CH2:17][CH2:16][N:15]([C:20]4[CH:28]=[C:27]5[C:23](=[C:22]([F:30])[CH:21]=4)[CH2:24][CH2:25][C:26]5=[O:29])[C:14]3=[O:18])=[CH:8][CH:7]=2)[CH2:3][CH2:1]1

참가 물질

4

반응물 2

HCID 509894266-Bromo-4-fluoro-2,3-dihydro-1H-inden-1-oneHCID 86715086(R)-3-((6-(cyclopropylmethoxy)pyridin-3-yl)oxy)pyrrolidin-2-one

생성물 1

HCID 73442850(R)-3-(6-Cyclopropylmethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

A mixture of (R)-3-[6-(2-cyclopropyl-methoxy)-pyridin-3-yloxy]-pyrrolidin-2-one (100 mg), 6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one (92 mg) and 1,4-dioxane (2 mL) was purged with argon. N,N′-Dimethyl-ethylene-diamine (355 mg), cesium carbonate (263 mg) and copper(I) iodide (8 mg) were added. The mixture was heated to 80° C. for 4 hours. After cooling to r.t. the mixture was filtered and the filtrate purified by preparative HPLC to provide Example 1-11. 1H-NMR (400 MHz, DMSO) δ 7.99 (1H, dd, J=11.2, 1.8 Hz), 7.95 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=9.0, 3.1 Hz), 6.79 (1H, d, J=9.0 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.03 (2H, d, J=7.1 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.10 (2H, m), 2.72 (2H, m), 2.68 (1H, m), 2.13 (1H, m), 1.22 (1H, m), 0.54 (2H, m), 0.30 (2H, m).

후처리

  1. customwas purged with argon
  2. additionN,N′-Dimethyl-ethylene-diamine (355 mg), cesium carbonate (263 mg) and copper(I) iodide (8 mg) were added
  3. temperatureAfter cooling to r.t. the mixture
  4. filtrationwas filtered
  5. customthe filtrate purified by preparative HPLC
  6. customto provide Example 1-11

출처 및 근거

ORD 기록
ord-d14ee5ebe67e402c8e7bfefbeb6d70b6
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08853412B2

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