Cesium carbonate → 6-(2-(Cyclopropanecarboxamido)pyridin-4-yloxy)quinoline-3-carboxylic acid

HRID 1894972Notes

Reaction equation

HRID 1894972 reaction equation
[N+]([C:4]1[CH:9]=[CH:8][N:7]=[C:6]([NH:10][C:11]([CH:13]2[CH2:15][CH2:14]2)=[O:12])[CH:5]=1)([O-])=O.[OH:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]=[CH:22][C:21]([C:27]([OH:29])=[O:28])=[CH:20]2.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH:13]1([C:11]([NH:10][C:6]2[CH:5]=[C:4]([O:16][C:17]3[CH:18]=[C:19]4[C:24](=[CH:25][CH:26]=3)[N:23]=[CH:22][C:21]([C:27]([OH:29])=[O:28])=[CH:20]4)[CH:9]=[CH:8][N:7]=2)=[O:12])[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 58902368N-(4-nitropyridin-2-yl)cyclopropanecarboxamideHCID 589024556-Hydroxyquinoline-3-carboxylic acid

Product 1

HCID 585256076-(2-(Cyclopropanecarboxamido)pyridin-4-yloxy)quinoline-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

N-(4-Nitropyridin-2-yl)cyclopropanecarboxamide (Int-23, 150 mg, 0.722 mmol), 6-hydroxyquinoline-3-carboxylic acid (Int-15, 150 mg, 0.794 mmol), and cesium carbonate (706 mg, 2.17 mmol) were weighed into a 2-5 mL microwave vial. N,N-dimethylformamide (3.5 mL) was added and the vial was capped. The reaction mixture was heated in the microwave for 3 h at 150° C. The vial was allowed to cool to room temperature and the cap was removed. The reaction mixture was diluted with water (5 mL) and stirred for a few minutes. The resulting clear solution was acidified by addition of 1N HCl and extracted three times with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. A solid precipitated in the extracts, was isolated by filtration and found to be the product. Solid product was combined with product isolated by extraction (0.245 g, 97%). LC-MS: (FA) ES+ 350; 1H NMR (400 MHz, d6-DMSO) δ ppm 13.67-13.47 (m, 1H), 10.92 (s, 1H), 9.30 (d, J=2.1 Hz, 1H), 8.98 (d, J=2.0 Hz, 1H), 8.25 (d, J=5.7 Hz, 1H), 8.21-8.17 (m, 1H), 8.01-7.99 (m, 1H), 7.75 (dd, J=9.1, 2.7 Hz, 1H), 7.70 (d, J=2.3 Hz, 1H), 6.81 (dd, J=5.7, 2.4 Hz, 1H), 1.95 (tt, J=7.6, 7.6, 4.9, 4.9 Hz, 1H), 0.81-0.67 (m, 4H).

Workup

  1. customthe vial was capped
  2. temperatureto cool to room temperature
  3. customthe cap was removed
  4. additionThe reaction mixture was diluted with water (5 mL)
  5. additionThe resulting clear solution was acidified by addition of 1N HCl
  6. extractionextracted three times with ethyl acetate
  7. washThe extracts were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customA solid precipitated in the extracts
  12. customwas isolated by filtration
  13. customisolated by extraction (0.245 g, 97%)

Sources & evidence

ORD record
ord-b9fdaaf9aba544c69a777ef80dc9b39e
Source dataset
uspto-grants-2013_08
Patent number
US08513421B2

Reaction notes

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