Hydrochloric Acid → 4-Amino-5-(3-(isopropylamino)-2,2-dimethyl-3-oxopropoxy)-2-methylquinoline-3-carboxylic acid

HRID 2410167Notes

Reaction equation

HRID 2410167 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([CH3:22])([CH3:21])[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[N:5]=[C:4]([CH3:23])[C:3]=1[C:24]([O:26]CC)=[O:25].[OH-].[Na+].Cl>CCO>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[O:12][CH2:13][C:14]([CH3:21])([CH3:22])[C:15]([NH:17][CH:18]([CH3:20])[CH3:19])=[O:16])[N:5]=[C:4]([CH3:23])[C:3]=1[C:24]([OH:26])=[O:25]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66746109HCID 66746109, compound

Product 1

HCID 667465594-Amino-5-(3-(isopropylamino)-2,2-dimethyl-3-oxopropoxy)-2-methylquinoline-3-carboxylic acidYield 89%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of ethyl 4-amino-5-(3-(isopropylamino)-2,2-dimethyl-3-oxopropoxy)-2-methylquinoline-3-carboxylate (Example 1a, 14.0 g, 36.2 mmol) in EtOH (140 mL) was added aqueous NaOH solution (2.0 N, 46 mL) at room temperature. The reaction mixture was stirred at 90° C. for 4 hrs. The resulting solution was neutralized at 0° C. to pH 7 with 6 N HCl, and concentrated under reduced pressure. The residue was re-dissolved in EtOH (400 mL) and water (25 mL), and treated with charcoal (200 mg) at 65° C. for 30 minutes. After removal of the charcoal by filtration, the filtrate was concentrated, and the resultant white solid was purified by re-crystallization from EtOH/H2O and dried under vacuum at 70° C. to give the title compound as a white solid (11.5 g, 89%). M.p.: 216-218° C. 1H NMR (400 MHz, DMSO-d6) δ 1.01 (d, J=6.4 Hz, 6H), 1.24 (s, 6H), 2.75 (s, 3H), 3.86-3.93 (m, 1H), 4.17 (s, 2H), 7.01 (d, J=8.0 Hz, 1H), 7.28 (d, J=8.4 Hz, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.67 (t, J=8.0 Hz, 1H), 8.83 (brs, 1H), 12.34 (brs, 1H), 12.78 (brs, 1H). MS 360 (MH+).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was re-dissolved in EtOH (400 mL)
  3. additionwater (25 mL), and treated with charcoal (200 mg) at 65° C. for 30 minutes
  4. customAfter removal of the charcoal
  5. filtrationby filtration
  6. concentrationthe filtrate was concentrated
  7. customthe resultant white solid was purified by re-crystallization from EtOH/H2O
  8. customdried under vacuum at 70° C.

Sources & evidence

ORD record
ord-db32df252b084568801a2e06c1772519
Source dataset
uspto-grants-2014_08
Patent number
US08815956B2

Reaction notes

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