Cesium carbonate → N-(4-(7-(4-oxaspiro[2.4]heptane-6-yloxy)quinolin-4-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide

HRID 2068220Notes

Reaction equation

HRID 2068220 reaction equation
[CH2:1]1[C:3]2([CH2:7][CH:6](CS([O-])(=O)=O)[CH2:5][O:4]2)[CH2:2]1.[OH:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18]([O:24][C:25]3[CH:30]=[CH:29][C:28]([N:31]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[C:32]([C:34]4([C:37]([NH2:39])=[O:38])[CH2:36][CH2:35]4)=[O:33])=[CH:27][C:26]=3[F:46])=[CH:19][CH:20]=[N:21]2)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C>[CH2:2]1[C:3]2([CH2:7][CH:6]([O:13][C:14]3[CH:23]=[C:22]4[C:17]([C:18]([O:24][C:25]5[CH:30]=[CH:29][C:28]([N:31]([C:40]6[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=6)[C:32]([C:34]6([C:37]([NH2:39])=[O:38])[CH2:36][CH2:35]6)=[O:33])=[CH:27][C:26]=5[F:46])=[CH:19][CH:20]=[N:21]4)=[CH:16][CH:15]=3)[CH2:5][O:4]2)[CH2:1]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 86640794HCID 86640794, compoundHCID 136347992N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide

Product 1

HCID 68635434N-(4-(7-(4-oxaspiro[2.4]heptane-6-yloxy)quinolin-4-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamideYield 20.1%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a mixture of (4-oxaspiro[2.4]heptane-6-yl)methanesulfonate (168 mg, 0.877 mmol, from example 6) and N-(4-(7-hydroxyquinolin-4-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamide (300 mg, 0.584 mmol) in 5 mL of N,N-dimethylacetamide was added cesium carbonate (893 mg, 2.74 mmol). After stirring at room temperature for 36 hrs, the reaction mixture was warmed up to 40° C. and continued to stir for 8 hrs. The reaction mixture was concentrated in vacuo and the residue was chromatographed with a silica gel column (1:1 (v/v) EtOAc/n-hexane) to afford the title compound as a white solid (65 mg, 18%).

Workup

  1. temperaturethe reaction mixture was warmed up to 40° C.
  2. stirringto stir for 8 hrs
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe residue was chromatographed with a silica gel column (1:1 (v/v) EtOAc/n-hexane)

Sources & evidence

ORD record
ord-2fe493cff5394c80a5624059542ca874
Source dataset
uspto-grants-2012_10
Patent number
US08293897B2

Reaction notes

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