Methyl iodide → HCID 54581661, compound

HRID 2088982Notes

Reaction equation

HRID 2088982 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:27])[C:5]([C:22]([O:24]CC)=[O:23])=[CH:6][N:7]2[CH2:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][N:17]=[CH:16]2.[CH3:28]I.[H-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:27])[C:5]([C:22]([OH:24])=[O:23])=[CH:6][N:7]2[CH2:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH3:28])[N:17]=[CH:16]2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58398106HCID 58398106, compound

Product 1

HCID 54581661HCID 54581661, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 5-fluoro-1-(1H-indazol-5-ylmethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (0.092 g, 0.25 mmol) in anhydrous N,N-dimethylformamide (0.8 mL) was added methyl iodide (0.10 mL, 1.60 mmol). The solution was cooled to 0° C. and sodium hydride (0.011 g, 0.28 mmol) was added. After stirring for 10 minutes at that temperature the reaction was quenched with water and 2 ml of a saturated aqueous lithium hydroxide solution was added. After stirring for 30 min, the solution was acidified with 4 N HCl and the product was extracted three times with EtOAc. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by reverse phase HPLC to provide the 5-fluoro-1-[(1-methyl-1H-indazol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. The 5-fluoro-1-[(2-methyl-2H-indazol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid was isolated as the minor product. 5-Fluoro-1-[(1-methyl-1H-indazol-5-yl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid gave a proton NMR spectrum consistent with theory and a mass ion (ES+) of 352 for M+H+. 1H NMR (400 MHz, CDCl3) δ 8.92 (s, 1H), 7.96 (s, 1H), 7.66-7.60 (m, 1H), 7.54 (s, 1H), 7.44 (d, J=8.7 Hz, 1H), 7.37 (d, J=8.7 Hz, 1H), 7.22-7.15 (m, 2H), 5.59 (s, 2H), 4.08 (s, 3H).

Workup

  1. customwas quenched with water and 2 ml of a saturated aqueous lithium hydroxide solution
  2. additionwas added
  3. stirringAfter stirring for 30 min
  4. extractionthe product was extracted three times with EtOAc
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-efa16eeb542342309519afafc89e6f27
Source dataset
uspto-grants-2013_05
Patent number
US08436016B2

Reaction notes

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