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

HRID 2068208Notes

Reaction equation

HRID 2068208 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:20]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:21]([C:23]2([C:26]([NH2:28])=[O:27])[CH2:25][CH2:24]2)=[O:22])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([OH:19])=[CH:16][CH:17]=2)[N:12]=[CH:11][CH:10]=1.CS(O[CH2:40][CH2:41][CH2:42][N:43]1[CH2:49][CH:48]([OH:50])[C:45]2([CH2:47][CH2:46]2)[CH2:44]1)(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>CC(N(C)C)=O>[OH:50][CH:48]1[C:45]2([CH2:47][CH2:46]2)[CH2:44][N:43]([CH2:42][CH2:41][CH2:40][O:19][C:15]2[CH:14]=[C:13]3[C:18]([C:9]([O:8][C:7]4[CH:6]=[CH:5][C:4]([N:20]([C:29]5[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=5)[C:21]([C:23]5([C:26]([NH2:28])=[O:27])[CH2:25][CH2:24]5)=[O:22])=[CH:3][C:2]=4[F:1])=[CH:10][CH:11]=[N:12]3)=[CH:17][CH:16]=2)[CH2:49]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 86640798HCID 86640798, compoundHCID 136347992N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide

Product 1

HCID 68635307N-(4-(7-(3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propoxy)quinolin-4-yloxy)-3-fluorophenyl)-N-phenylcyclopropane-1,1-dicarboxamideYield 53%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-(3-fluoro-4-(7-hydroxyquinolin-4-yloxy)phenyl)-N-phenylcyclopropane-1,1-dicarboxamide (240 mg, 0.525 mmol) in DMA (3 mL) was added 3-(7-hydroxy-5-azaspiro[2.4]heptane-5-yl)propyl methanesulfonate (261 mg, 1.05 mmol) and Cs2CO3 (512 mg, 1.575 mmol). The reaction was then stirred at rt for 24 hrs. The solvent was removed and the residue was partioned between saturated NaHCO3 (10 mL) aqueous solution and CHCl3 (30 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered and 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 white solid (170 mg, 53%).

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-95456c808b3f4417ad9386eaeb264c84
Source dataset
uspto-grants-2012_10
Patent number
US08293897B2

Reaction notes

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