Sodium Hydroxide → Ethyl 6-chloro-4-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)quinoline-3-carboxylate

HRID 1944603Notes

Reaction equation

HRID 1944603 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][N:28]([C:31](=[O:34])[CH2:32][CH3:33])[CH2:27][CH2:26]2)=[C:21]([C:35]([F:38])([F:37])[F:36])[CH:20]=1.[OH-].[Na+]>O1CCOCC1.CCOC(C)=O>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][C:3]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:2]2[NH:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:30][CH2:29][N:28]([C:31](=[O:34])[CH2:32][CH3:33])[CH2:27][CH2:26]2)=[C:21]([C:35]([F:38])([F:37])[F:36])[CH:20]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 1479087Ethyl 4,6-dichloroquinoline-3-carboxylateHCID 585251011-(4-(4-Amino-2-(trifluoromethyl)phenyl)piperazin-1-yl)propan-1-one

Product 1

HCID 58525139Ethyl 6-chloro-4-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)quinoline-3-carboxylateYield 93.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5.0 ethyl 4,6-dichloroquinoline-3-carboxylate (1.08 g, 4 mmol, 1 equiv.) in 1,4-dioxane (10 mL) at room temperature was added compound 5.1 1-(4-(4-amino-2-(trifluoromethyl)phenyl)piperazin-1-yl)propan-1-one (1.2 g, 4 mmol, 1 equiv.). The resulting solution was heated to 80° C. and stirred 4 h before cooling to room temperature. NaOH ON aqueous solution, 3 mL) was added. The solution was diluted with EtOAc (30 mL) and washed with water (30 mL×2) and brine (30 mL). The organic phase was dried over Na2SO4. After removal of solvents, the residue was purified via flash chromatography (CH2Cl2: MeOH=20:1) to afford the desired product 5.2 ethyl 6-chloro-4-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)quinoline-3-carboxylate (2 g; 93%). LC-MS: (M+H): 622.20

Workup

  1. temperaturebefore cooling to room temperature
  2. washwashed with water (30 mL×2) and brine (30 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. customAfter removal of solvents
  5. customthe residue was purified via flash chromatography (CH2Cl2: MeOH=20:1)

Sources & evidence

ORD record
ord-1e24efbee4ac41df85c789f8d2550aa3
Source dataset
uspto-grants-2013_03
Patent number
US08394818B2

Reaction notes

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