Triethylamine → 5-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoline-8-carboxylic acid [4-(4-ethyl-piperazin-1-yl)-phenyl]-amide

HRID 1189876Notes

Reaction equation

HRID 1189876 reaction equation
CCCP(=O)=O.[Cl:7][C:8]1[C:13]([O:14][CH3:15])=[CH:12][C:11]([O:16][CH3:17])=[C:10]([Cl:18])[C:9]=1[C:19]1[CH:28]=[CH:27][C:26]([C:29](O)=[O:30])=[C:25]2[C:20]=1[CH:21]=[CH:22][CH:23]=[N:24]2.[CH2:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[CH:46]=[CH:45][C:43]([NH2:44])=[CH:42][CH:41]=2)[CH2:36][CH2:35]1)[CH3:33].CCN(CC)CC>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O.O>[CH2:32]([N:34]1[CH2:35][CH2:36][N:37]([C:40]2[CH:46]=[CH:45][C:43]([NH:44][C:29]([C:26]3[CH:27]=[CH:28][C:19]([C:9]4[C:10]([Cl:18])=[C:11]([O:16][CH3:17])[CH:12]=[C:13]([O:14][CH3:15])[C:8]=4[Cl:7])=[C:20]4[C:25]=3[N:24]=[CH:23][CH:22]=[CH:21]4)=[O:30])=[CH:42][CH:41]=2)[CH2:38][CH2:39]1)[CH3:33]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 9367384-(4-Ethylpiperazin-1-yl)anilineHCID 16167369Propylphosphoric anhydrideHCID 592929115-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoline-8-carboxylic acid

Product 1

HCID 592928475-(2,6-Dichloro-3,5-dimethoxy-phenyl)-quinoline-8-carboxylic acid [4-(4-ethyl-piperazin-1-yl)-phenyl]-amide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of propylphosphonic anhydride (50% in DMF, 0.41 mL, 0.70 mmol, 2 equiv), 5-(2,6-dichloro-3,5-dimethoxy-phenyl)-quinoline-8-carboxylic acid (Step 159.1) (132 mg, 0.35 mmol), 4-(4-ethylpiperazin-1-yl)-aniline (Step 1.9) (79 mg, 0.39 mmol, 1.1 equiv), DMAP (3 mg), and Et3N (0.49 mL, 3.5 mmol, 10 equiv) in DMF (3 mL), was stirred for 16 h at rt, under an argon atmosphere. The reaction mixture was diluted with EtOAc and H2O. The aqueous layer was separated and extracted with EtOAc. The combined organic phase was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by trituration in EtOAc to afford the title compound as a yellow solid: ES-MS: 564.9/566.9 [M+H]+; tR=4.45 min (System 1).

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with EtOAc
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by trituration in EtOAc

Sources & evidence

ORD record
ord-189e7941b6f84ce7bc82b5e13dd0d3c0
Source dataset
uspto-grants-2014_03
Patent number
US08674099B2

Reaction notes

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