Cesium carbonate → N-(5-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)quinolin-4-yloxy)pyridin-2-yl)-N-phenylcyclopropane-1,1-dicarboxamide

HRID 2068211Notes

Reaction equation

HRID 2068211 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[CH:15][C:16]([N:19]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:20]([C:22]4([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]4)=[O:21])=[N:17][CH:18]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.CS(O[CH2:39][CH2:40][CH2:41][N:42]1[CH2:48][CH:47]([OH:49])[C:44]2([CH2:46][CH2:45]2)[CH2:43]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[OH:49][CH:47]1[C:44]2([CH2:46][CH2:45]2)[CH2:43][N:42]([CH2:41][CH2:40][CH2:39][O:1][C:2]2[CH:11]=[C:10]3[C:5]([C:6]([O:12][C:13]4[CH:14]=[CH:15][C:16]([N:19]([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=5)[C:20]([C:22]5([C:25]([NH2:27])=[O:26])[CH2:24][CH2:23]5)=[O:21])=[N:17][CH:18]=4)=[CH:7][CH:8]=[N:9]3)=[CH:4][CH:3]=2)[CH2:48]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 86640798HCID 86640798, compoundHCID 136381440N-(5-(7-hydroxyquinolin-4-yloxy)pyridin-2-yl)-N-phenylcyclopropane-1,1-dicarboxamide

Product 1

HCID 68636289N-(5-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)quinolin-4-yloxy)pyridin-2-yl)-N-phenylcyclopropane-1,1-dicarboxamideYield 75%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-(5-(7-hydroxyquinolin-4-yloxy)pyridin-2-yl)-N-phenylcyclopropane-1,1-dicarboxamide (110 mg, 0.25 mmol) in DMA (2 mL) was added 3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propyl methanesulfonate (125 mg, 0.50 mmol) and Cs2CO3 (243 mg, 0.75 mmol). The reaction was then stirred at rt for 24 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 the filtrate was concentrated in vacuo. 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 (110 mg, 75%).

Workup

  1. customThe solvent was removed
  2. customThe organic layer was separated
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated 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-4ac30370f30241cea613bf9c548e1495
Source dataset
uspto-grants-2012_10
Patent number
US08293897B2

Reaction notes

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