Cesium carbonate → N-(3-fluoro-4-(7-(3-(1-hydroxycyclopropyl)propoxy)quinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 1517868Notes

Reaction equation

HRID 1517868 reaction equation
CS([O:5][CH2:6][CH2:7][CH2:8][C:9]1([OH:12])[CH2:11][CH2:10]1)(=O)=O.[F:13][C:14]1[CH:15]=[C:16]([NH:32][C:33]([C:35]2[C:36](=[O:48])[N:37]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:38]([CH3:41])[C:39]=2[CH3:40])=[O:34])[CH:17]=[CH:18][C:19]=1[O:20][C:21]1[C:30]2[C:25](=[CH:26][C:27](O)=[CH:28][CH:29]=2)[N:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C.O>[F:13][C:14]1[CH:15]=[C:16]([NH:32][C:33]([C:35]2[C:36](=[O:48])[N:37]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[N:38]([CH3:41])[C:39]=2[CH3:40])=[O:34])[CH:17]=[CH:18][C:19]=1[O:20][C:21]1[C:30]2[C:25](=[CH:26][C:27]([O:5][CH2:6][CH2:7][CH2:8][C:9]3([OH:12])[CH2:11][CH2:10]3)=[CH:28][CH:29]=2)[N:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 86640796HCID 86640796, compoundHCID 136347997N-(3-fluoro-4-((7-hydroxyquinolin-4-yl)oxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 46201942N-(3-fluoro-4-(7-(3-(1-hydroxycyclopropyl)propoxy)quinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 19%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a mixture of 3-(1-hydroxycyclopropyl)propyl methanesulfonate (240 mg, 1.2 mmol) and N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (300 mg, 0.62 mmol) in 5 mL of N,N-dimethylacetamide was added cesium carbonate (470 mg, 2.4 mmol). After stirring at rt for 12 hrs, then the mixture was warmed up to 40° C. and stirred for 6 hrs. The reaction mixture was diluted with 20 mL of water and extracted with ethyl acetate (40 mL×3). The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (5:1 (v/v) EtOAc/n-hexane) to afford the desired compound as a white solid (68 mg, 19%).

Workup

  1. temperaturethe mixture was warmed up to 40° C.
  2. stirringstirred for 6 hrs
  3. extractionextracted with ethyl acetate (40 mL×3)
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a silica gel column chromatography (5:1 (v/v) EtOAc/n-hexane)

Sources & evidence

ORD record
ord-b0636c9366ec4049a899404feff7dd37
Source dataset
uspto-grants-2012_07
Patent number
US08232294B2

Reaction notes

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