Tetrahydrofuran → HCID 10594477, compound

HRID 977170Notes

Reaction equation

HRID 977170 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[NH:5][C:4](=[O:13])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[H-].[Na+].C([CH:24]([C:28](Cl)=[O:29])[C:25](Cl)=[O:26])C.[O:31]1CCCC1>>[C:28]([CH2:24][C:25]([NH:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:12])=[CH:9][CH:10]=2)[NH:5][C:4](=[O:13])[C:3]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:26])([OH:29])=[O:31]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 10707207HCID 10707207, compoundHCID 109209242-Ethylpropanedioyl dichloride

Product 1

HCID 10594477HCID 10594477, compound

Conditions

Temperature
60 °C

Procedure

A solution of 4-amino-7-chloro-3-phenyl-2(1H)-quinolone (Example 2) (0.5 g) in 50 ml tetrahydrofuran was stirred under an atmosphere of nitrogen and treated with sodium hydride (0.3 g, 80% disp. in mineral oil). This was followed by the addition after 1 h of ethyl malonyl chloride (1.8 ml). The reaction mixture was heated at 60° C. for 14 h, cooled and partitioned between ethyl acetate and water. The organic phase was washed with water (2×) before the solvent was removed in vacuo. The residue was saponified using 4N sodium hydroxide lo (100 ml) and ultrasound. The solution was adjusted to pill using conc. HCl then extracted into ethyl acetate, dried (MgSO4) and the solvent was removed in vacuo. The residue was purified by preparative HPLC followed by recrystallisation from DMF-water to give the title compound (50 mg); mp 260° C. decomposed; δ (360 MHz, DMSO) 3.22 (2H, s, CH2CO2H), 7.22-7.76 (7H, m, aromatics), 7.87 (1H, d, 5-H, J=8.4 Hz), 9.97 (1H, s, NHCOCH2CO2H), 12.13 (1H, s, NH). Found: C, 60.29; H, 3.83; N, 7.69. C18H13N2O4Cl requires C, 60.60; H, 3.67; N, 7.85%.

Workup

  1. temperaturecooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organic phase was washed with water (2×) before the solvent
  4. customwas removed in vacuo
  5. extractionthen extracted into ethyl acetate
  6. dry with materialdried (MgSO4)
  7. customthe solvent was removed in vacuo
  8. customThe residue was purified by preparative HPLC
  9. customfollowed by recrystallisation from DMF-water

Sources & evidence

ORD record
ord-7652bac4a5494cbb9f3d5dfd5add92ee
Source dataset
uspto-grants-1997_03
Patent number
US05614532

Reaction notes

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