Acetyl chloride → 1-(4-(3-((1-(Quinolin-2-yl)piperidin-4-yl)oxy)pyrazin-2-yl)piperazin-1-yl)ethanone

HRID 454924Notes

Reaction equation

HRID 454924 reaction equation
[N:1]1([C:7]2[C:8]([O:13][CH:14]3[CH2:19][CH2:18][N:17]([C:20]4[CH:29]=[CH:28][C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[N:21]=4)[CH2:16][CH2:15]3)=[N:9][CH:10]=[CH:11][N:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.CCN(CC)CC.[C:37](Cl)(=[O:39])[CH3:38]>C(Cl)Cl>[N:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:28]=[CH:29][C:20]=1[N:17]1[CH2:18][CH2:19][CH:14]([O:13][C:8]2[C:7]([N:1]3[CH2:2][CH2:3][N:4]([C:37](=[O:39])[CH3:38])[CH2:5][CH2:6]3)=[N:12][CH:11]=[CH:10][N:9]=2)[CH2:15][CH2:16]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 674774332-(4-((3-(Piperazin-1-YL)pyrazin-2-YL)oxy)piperidin-1-YL)quinoline

Product 1

HCID 546706721-(4-(3-((1-(Quinolin-2-yl)piperidin-4-yl)oxy)pyrazin-2-yl)piperazin-1-yl)ethanoneYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4-((3-(piperazin-1-yl)pyrazin-2-yl)oxy)piperidin-1-yl)quinoline (130 mg, 0.33 mmol) in dry DCM (10 mL) was added Et3N (1 mL). The reaction mixture was cooled to 0° C. with an ice bath, and acetyl chloride (80 mg, 0.66 mmol) was added dropped to the reaction mixture. 1 hour later, the reaction mixture was warmed to RT, and stirred overnight. Then the reaction mixture was washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum to give the crude product. The crude product was purified via flash chromatography on silica gel (20% to 45% EtOAc in petroleum ether) to give 1-(4-(3-((1-(quinolin-2-yl)piperidin-4-yl)oxy)pyrazin-2-yl)piperazin-1-yl)ethanone (108 mg, 0.25 mmol, 78% yield) as a white solid. ESI-MS (M+1): 433 calc. for C24H28N6O2 432.

Workup

  1. additiondropped to the reaction mixture
  2. temperature1 hour later, the reaction mixture was warmed to RT
  3. washThen the reaction mixture was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto give the crude product
  8. customThe crude product was purified via flash chromatography on silica gel (20% to 45% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-8210c0522deb4491a7693b2ad20d7848
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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