Cesium carbonate → N-(4-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)-6-methoxyquinolin-4-yloxy)-3-fluorophenyl)-2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazole-4-carboxamide

HRID 1969414Notes

Reaction equation

HRID 1969414 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:22][C:23]([C:25]2[C:26](=[O:38])[N:27]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[N:28]([CH3:31])[C:29]=2[CH3:30])=[O:24])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([OH:21])=[C:16]([O:19][CH3:20])[CH:17]=2)[N:12]=[CH:11][CH:10]=1.CS(O[CH2:44][CH2:45][CH2:46][N:47]1[CH2:53][CH:52]([OH:54])[C:49]2([CH2:51][CH2:50]2)[CH2:48]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[OH:54][CH:52]1[C:49]2([CH2:51][CH2:50]2)[CH2:48][N:47]([CH2:46][CH2:45][CH2:44][O:21][C:15]2[CH:14]=[C:13]3[C:18]([C:9]([O:8][C:7]4[CH:6]=[CH:5][C:4]([NH:22][C:23]([C:25]5[C:26](=[O:38])[N:27]([C:32]6[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=6)[N:28]([CH3:31])[C:29]=5[CH3:30])=[O:24])=[CH:3][C:2]=4[F:1])=[CH:10][CH:11]=[N:12]3)=[CH:17][C:16]=2[O:19][CH3:20])[CH2:53]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 86640798HCID 86640798, compoundHCID 136341072N-(3-fluoro-4-(7-hydroxy-6-methoxyquinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

Product 1

HCID 46202279N-(4-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)-6-methoxyquinolin-4-yloxy)-3-fluorophenyl)-2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazole-4-carboxamideYield 66%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-(3-fluoro-4-(7-hydroxy-6-methoxyquinolin-4-yloxy)phenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (200 mg, 0.389 mmol) in DMA (2 mL) was added 3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propyl methanesulfonate (193 mg, 0.778 mmol) and Cs2CO3 (379 mg, 1.167 mmol). The reaction was then stirred at rt for 40 hrs. The solvent was removed and the residue was partioned between saturated NaHCO3 aqueous solution (10 mL) and CHCl3 (30 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated in vacuo and the residue was purified by a silica gel column chromatography (100:15:1 (v/v/v) EtOAc/CH3OH/Et3N) to afford the desired compound as a pale yellow solid (171 mg, 66%).

Workup

  1. customThe solvent was removed
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customthe residue was purified by a silica gel column chromatography (100:15:1 (v/v/v) EtOAc/CH3OH/Et3N)

Sources & evidence

ORD record
ord-efd54c747fcf490aa580a9e5b59e2ab3
Source dataset
uspto-grants-2013_04
Patent number
US08426585B2

Reaction notes

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