4-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamine → N-[4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluoro-phenyl]-4-ethoxy-1-(4-fluorophenyl)pyrazole-3-carboxamide

HRID 1465187Notes

Reaction equation

HRID 1465187 reaction equation
[CH2:1]([O:3][C:4]1[C:5]([C:16](Cl)=[O:17])=[N:6][N:7]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)[CH:8]=1)[CH3:2].[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][C:30]=1[O:31][CH3:32])[N:27]=[CH:26][CH:25]=[C:24]2[O:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][C:35]=1[F:41]>N1C=CC=CC=1.CCOC(C)=O>[CH3:19][O:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][C:30]=1[O:31][CH3:32])[N:27]=[CH:26][CH:25]=[C:24]2[O:33][C:34]1[CH:40]=[CH:39][C:37]([NH:38][C:16]([C:5]2[C:4]([O:3][CH2:1][CH3:2])=[CH:8][N:7]([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[N:6]=2)=[O:17])=[CH:36][C:35]=1[F:41]

Participants

5

Reactant 2

HCID 114269974-((6,7-Dimethoxyquinolin-4-yl)oxy)-3-fluorobenzenamineHCID 867081584-Ethoxy-1-(4-fluorophenyl)pyrazole-3-carbonyl chloride

Product 1

HCID 56847425N-[4-[(6,7-dimethoxy-4-quinolyl)oxy]-3-fluoro-phenyl]-4-ethoxy-1-(4-fluorophenyl)pyrazole-3-carboxamideYield 52%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

Acid chloride D4 (0.17 mmol, 1.0 eq.) was dissolved in dry pyridine (1.5 mL) at 0° C. and A2 (34 mg, 0.11 mmol, 0.65 eq.) was added. The reaction was allowed to reach RT overnight. The mixture was diluted with EtOAc and washed twice with aq. KOH-solution (0.5N), twice with aq. sat. NH4Cl-solution, and finally once with brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (DCM/MeOH=100:0 to 10:1) to yield the desired product D5 (31 mg, 52% over 2 steps) as a white solid. 1H NMR (400 MHz, d6-DMSO, 300K) δ 1.38 (t, J=7.0 Hz, 3H), 3.94 (s, 6H), 4.09 (q, J=7.0 Hz, 2H), 6.48 (d, J=5.3 Hz, 1H), 7.43 (m, 4H), 7.53 (s, 1H), 7.70 (d, J=9.4 Hz, 1H), 8.01 (m, 3H), 8.47 (m, 2H), 10.17 (s, 1H). MS (ES) C29H24F2N4O5 requires: 546. Found: 547 (M+H)+.

Workup

  1. washwashed twice with aq. KOH-solution (0.5N), twice with aq. sat. NH4Cl-solution
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by flash chromatography on silica gel (DCM/MeOH=100:0 to 10:1)

Sources & evidence

ORD record
ord-05d69ea5bb8b4113a6faa4acc3c0f94d
Source dataset
uspto-grants-2015_04
Patent number
US08999982B2

Reaction notes

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