Hydrochloric Acid → HCID 178493637, compound

HRID 2289955Notes

Reaction equation

HRID 2289955 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:21](=[O:22])[C:20]3[C:15](=[C:16]([F:26])[C:17]([O:24][CH3:25])=[C:18]([F:23])[CH:19]=3)[N:14](COCC[Si](C)(C)C)[CH:13]=2)=[O:11])=[CH:4][CH:3]=1.Cl.C(=O)(O)[O-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18]([F:23])=[C:17]([O:24][CH3:25])[C:16]=3[F:26])=[O:11])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 18698673HCID 18698673, compound

Product 1

HCID 178493637HCID 178493637, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

N-((4-Chlorophenyl)methyl)-4-oxo-6,7,8-trifluoro-1-(2-(trimethylsilyl)ethoxy) methyl-3-quinolinecarboxamide (1.00 g) from Preparation No. 13 and methanol (163 μL) are dissolved in DMF (20 mL). Sodium hydride (60% dispersion, 80 mg) is added and the mixture is heated to 140° C. for 1 h. The mixture is allowed to cool to rt, is poured into sat. aq. ammonium chloride (100 mL), and is extracted with ethyl acetate (3×50 mL). The organic layer is washed with brine (10 mL), dried (MgSO4), and concentrated. The crude product is purified by column chromatography (heptane/ethyl acetate, 4/1; 3/1) to afford N-((4-chlorophenyl)methyl)-6,8-difluoro-7-methoxy-4-oxo-1-(2-(trimethylsilyl)ethoxy)methyl-3-quinolinecarboxamide. The resulting crude amide is suspended in ethanol (15 mL), heated to 85° C., and to the mixture is added 50% aq. hydrochloric acid (5 mL). The mixture is heated an additional 1.5 h and allowed to cool to rt. The reaction mixture is neutralized with solid sodium bicarbonate and filtered. The solids are washed with ethanol (10 mL) followed by ethyl acetate (20 mL), and the combined filtrates are concentrated to afford a tan solid. The crude product is purified by recrystallization from acetic acid/water followed by column chromatography (heptane/2-propanol, 95/5) to afford 27 mg of the title compound.

Workup

  1. temperatureThe mixture is heated an additional 1.5 h
  2. temperatureto cool to rt
  3. filtrationfiltered
  4. washThe solids are washed with ethanol (10 mL)
  5. concentrationthe combined filtrates are concentrated
  6. customto afford a tan solid
  7. customThe crude product is purified by recrystallization from acetic acid/water

Sources & evidence

ORD record
ord-8196a52620f74ffaa2e7392b8a0e94bc
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

Loading…