Acetyl chloride → 1-(4-{4-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidin-1-yl)-ethanone

HRID 69252ノート

反応式

HRID 69252 の反応式
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1.C(N(CC)CC)C.[C:40](Cl)(=[O:42])[CH3:41]>C1COCC1.CCOC(C)=O>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[CH2:12][C:13]1[N:17]2[N:18]=[C:19]([C:22]3[CH:23]=[N:24][N:25]([CH:27]4[CH2:32][CH2:31][N:30]([C:40](=[O:42])[CH3:41])[CH2:29][CH2:28]4)[CH:26]=3)[CH:20]=[CH:21][C:16]2=[N:15][CH:14]=1

参加物

6

反応物 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 579174297-fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline

生成物 1

HCID 579174781-(4-{4-[3-(7-Fluoro-quinolin-6-ylmethyl)-imidazo[1,2-b]pyridazin-6-yl]-pyrazol-1-yl}-piperidin-1-yl)-ethanone

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

7-Fluoro-6-[6-(1-piperidin-4-yl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazin-3-ylmethyl]-quinoline (Example 180, 50 mg, 0.117 mmol) and triethylamine (33 μL, 0.234 mmol) were dissolved in THF (1 mL). Acetyl chloride (9 mg, 0.117 mmol) was then added dropwise and the mixture was stirred at rt for 2 h. The mixture was diluted with EtOAc and washed with NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with a 4 g RediSep® silica gel column, DCM/(DCM/MeOH 9:1+NH3)=100:0→0:100) to afford the title compound as a foam (tR 3.50 min (conditions 3), MH+=470.2, 1H-NMR in DMSO-d6: 8.84 (m, 1H); 8.51 (s, 1H); 8.34 (m, 1H); 8.09 (m, 2H); 8.04 (d, 1H); 7.76 (d, 1H); 7.60 (s, 1H); 7.53 (d, 1H); 7.47 (dd, 1H); 4.55 (s, 2H); 4.48 (m, 2H); 3.92 (m, 1H); 3.21 (m, 1H); 2.72 (m, 1H); 2.04 (m, 5H); 1.89 (m, 1H); 1.75 (m, 1H)).

後処理

  1. washwashed with NaHCO3 and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (CombiFlash® Companion System®

出典と根拠

ORDレコード
ord-c7365f57473a43b5b7bdfca2ed438340
出典データセット
uspto-grants-2014_09
特許番号
US08822468B2

反応ノート

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