Triethylamine → 4'-chloro-N-{3-[(diethylamino)methyl]-6-methoxy-7-quinolinyl}[1,1'-biphenyl]-4-carboxamide

HRID 351349

Reaction equation

HRID 351349 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH2:23]([N:25]([CH2:28][C:29]1[CH:30]=[N:31][C:32]2[C:37]([CH:38]=1)=[CH:36][C:35]([O:39][CH3:40])=[C:34]([NH2:41])[CH:33]=2)[CH2:26][CH3:27])[CH3:24].C(N(CC)CC)C>O1CCCC1.CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([NH:41][C:34]3[CH:33]=[C:32]4[C:37]([CH:38]=[C:29]([CH2:28][N:25]([CH2:26][CH3:27])[CH2:23][CH3:24])[CH:30]=[N:31]4)=[CH:36][C:35]=3[O:39][CH3:40])=[O:16])=[CH:12][CH:13]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 6160024-Biphenylcarboxylic acid, 4'-chloro-HCID 184359423-[(Diethylamino)methyl]-6-methoxy-7-quinolinylamine

Product 1

HCID 184360584'-chloro-N-{3-[(diethylamino)methyl]-6-methoxy-7-quinolinyl}[1,1'-biphenyl]-4-carboxamideYield 13.5%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4′-Chloro[1,1′-biphenyl]-4-carboxylic acid (100 mg, 0.430 mmol) was dissolved in tetrahydrofuran (5 ml). To the reaction solution were added oxalyl chloride (0.0375 ml, 0.430 mmol) and one drop of DMF, and the mixture was stirred at room temperature for 1.5 hrs. The reaction solution was concentrated under reduced pressure and the obtained pale-brown crystals were dissolved in DMF (1 ml). Thereto were added a solution of 3-[(diethylamino)methyl]-6-methoxy-7-quinolinylamine (111 mg, 0.430 mmol) obtained in Reference Example 13 in DMF (1 ml) and triethylamine (0.0719 ml, 0.516 mmol), and the mixture was stirred at room temperature for 4 hrs. Ethyl acetate (20 ml) was added to the reaction solution, and the mixture was washed with a mixed solution of aqueous potassium carbonate solution (10 ml) and saturated brine (5 ml), and then with a mixed solution of saturated brine (10 ml) and water (10 ml). The organic layer was purified by NH-silica gel column, and the precipitated crystals were washed with ethyl acetate:isopropyl ether=2:1. The crystals were collected by filtration and dried to give the title compound (27.5 mg) as pale-yellow crystals.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. dissolutionthe obtained pale-brown crystals were dissolved in DMF (1 ml)
  3. washthe mixture was washed with a mixed solution of aqueous potassium carbonate solution (10 ml) and saturated brine (5 ml)
  4. customThe organic layer was purified by NH-silica gel column
  5. washthe precipitated crystals were washed with ethyl acetate
  6. filtrationThe crystals were collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-51f39c8bf894482a9608cf77ec3a671b
Source dataset
uspto-grants-2007_02
Patent number
US07183415B2

Linked notes

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