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 533891ノート

反応式

HRID 533891 の反応式
[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

参加物

4

反応物 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

生成物 1

HCID 73442850(R)-3-(6-Cyclopropylmethoxy-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
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-d14ee5ebe67e402c8e7bfefbeb6d70b6
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…