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 69252Notes

Reaction equation

HRID 69252 reaction equation
[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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)).

Workup

  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®

Sources & evidence

ORD record
ord-c7365f57473a43b5b7bdfca2ed438340
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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