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 1969400Notes

Reaction equation

HRID 1969400 reaction equation
CS([O:5][CH2:6][CH2:7][CH2:8][C:9]1([OH:12])[CH2:11][CH2:10]1)(=O)=O.O[C:14]1[CH:23]=[C:22]2[C:17]([C:18]([O:24][C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:32]([C:34]4[C:35](=[O:47])[N:36]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=5)[N:37]([CH3:40])[C:38]=4[CH3:39])=[O:33])=[CH:27][C:26]=3[F:48])=[CH:19][CH:20]=[N:21]2)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C.O>[F:48][C:26]1[CH:27]=[C:28]([NH:31][C:32]([C:34]2[C:35](=[O:47])[N:36]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[N:37]([CH3:40])[C:38]=2[CH3:39])=[O:33])[CH:29]=[CH:30][C:25]=1[O:24][C:18]1[C:17]2[C:22](=[CH:23][C:14]([O:5][CH2:6][CH2:7][CH2:8][C:9]3([OH:12])[CH2:11][CH2:10]3)=[CH:15][CH:16]=2)[N:21]=[CH:20][CH:19]=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-(4-(7-hydroxyquinolin-4-yloxy)-3-fluorophenyl)-2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-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, Aladdin). After stirring at rt for 12 hrs, the reaction mixture was warmed to 40° C. and stirred for additional 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, concentrated in vacuo and chromatographed with a silica gel column (5:1 (v/v) EtOAc/n-Hexane) to provide the title compound as a white solid (68 mg, 19%).

Workup

  1. temperaturethe reaction mixture was warmed to 40° C.
  2. stirringstirred for additional 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. customchromatographed with a silica gel column (5:1 (v/v) EtOAc/n-Hexane)

Sources & evidence

ORD record
ord-c199e8f2225a48a885e65d793e5d0587
Source dataset
uspto-grants-2013_04
Patent number
US08426585B2

Reaction notes

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