Sodium Carbonate → Ethyl 4'-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylate

HRID 1944604Notes

Reaction equation

HRID 1944604 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:5]2[NH:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:29][CH2:28][N:27]([C:30](=[O:33])[CH2:31][CH3:32])[CH2:26][CH2:25]2)=[C:20]([C:34]([F:37])([F:36])[F:35])[CH:19]=1.B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[C:30]([N:27]1[CH2:28][CH2:29][N:24]([C:21]2[CH:22]=[CH:23][C:18]([NH:17][C:5]3[C:4]4[C:9](=[CH:10][CH:11]=[C:2]([C:6]5[CH:7]=[N:8][C:9]6[C:4]([CH:5]=5)=[CH:3][CH:2]=[CH:11][CH:10]=6)[CH:3]=4)[N:8]=[CH:7][C:6]=3[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:19][C:20]=2[C:34]([F:37])([F:35])[F:36])[CH2:25][CH2:26]1)(=[O:33])[CH2:31][CH3:32]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 61668Boronic AcidHCID 58525139Ethyl 6-chloro-4-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)quinoline-3-carboxylate

Product 1

HCID 49782829Ethyl 4'-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6'-biquinoline-3'-carboxylateYield 71.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of compound 5.2 ethyl 6-chloro-4-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)quinoline-3-carboxylate (1 g, 1.6 mmol, 1 equiv.) in dioxane (5 mL) at room temperature was sequentially added 3-qunionline boronic acid 5.3 (350 mg, 2 mmol, 1.1 equiv.), PdCl2(Ph3P)2 (130 mg, 0.19 mmol, 0.1 equiv.), t-Bu-Xphos (78 mg, 0.19 mmol, 0.1 equiv.) and Na2CO3 (1N, 5.5 mL, 5.5 mmol, 3 equiv.). The mixture was degassed, sealed under argon, and heated overnight at 100° C. Upon cooling to room temperature, the mixture was diluted with EtOAc (20 mL), filtered through celite, and washed with EtOAc (20 mL×2). The resulting solution was concentrated and the residue was purified via flash chromagraphy (CH2Cl2: MeOH=30:1) to afford the desired product 5.4 ethyl 4′-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenylamino)-3,6′-biquinoline-3′-carboxylate (360 mg; 31%). LC-MS: (M+H): 535.20

Workup

  1. customThe mixture was degassed
  2. customsealed under argon
  3. temperatureUpon cooling to room temperature
  4. additionthe mixture was diluted with EtOAc (20 mL)
  5. filtrationfiltered through celite
  6. washwashed with EtOAc (20 mL×2)
  7. concentrationThe resulting solution was concentrated
  8. customthe residue was purified via flash chromagraphy (CH2Cl2: MeOH=30:1)

Sources & evidence

ORD record
ord-51632f83cd8140d6ac8c44bb5ccd0025
Source dataset
uspto-grants-2013_03
Patent number
US08394818B2

Reaction notes

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