Hydrochloric Acid → (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

HRID 2061804Notes

Reaction equation

HRID 2061804 reaction equation
[CH2:1]([NH:3][C:4](=[O:41])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[N:18]([C@@H:22]([CH3:25])[CH2:23][OH:24])[CH:17]=[C:16]([C:26]([O:28]CC)=[O:27])[C:15]3=[O:31])=[C:8]([C:32]2[S:33][CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[N:36]=2)[CH:7]=1)[CH3:2].[OH-].[Li+].Cl>O1CCCC1.CO.O>[CH2:1]([NH:3][C:4](=[O:41])[NH:5][C:6]1[N:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[N:18]([C@@H:22]([CH3:25])[CH2:23][OH:24])[CH:17]=[C:16]([C:26]([OH:28])=[O:27])[C:15]3=[O:31])=[C:8]([C:32]2[S:33][CH:34]=[C:35]([C:37]([F:39])([F:40])[F:38])[N:36]=2)[CH:7]=1)[CH3:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59416119(S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

Product 1

HCID 59415946(S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acidYield 48.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Example 97, 200 mg, 0.34 mmol, 1 equiv.) in tetrahydrofuran (1 mL) and methanol (1 mL) was added 2 M lithium hydroxide (0.339 mL). The mixture was stirred in the microwave at 100° C. for 15 min The reaction mixture was cooled to room temperature and diluted with water. 1 N HCl was added until pH 3-4 was reached. The reaction mixture was partitioned between ethyl acetate (5 mL) and water (5 mL). The aqueous layer was extracted with ethyl acetate (2×5 mL), and the organics were washed with brine (10 mL), dried over sodium sulfate, and concentrated under reduced pressure. Purification via reverse phase HPLC (C18 column, acetonitrile/water 0-95% gradient) and concentrated under reduced pressure to provide (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxypropan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (92 mg, 48%).

Workup

  1. temperaturewas cooled to room temperature
  2. customThe reaction mixture was partitioned between ethyl acetate (5 mL) and water (5 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×5 mL)
  4. washthe organics were washed with brine (10 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification via reverse phase HPLC (C18 column, acetonitrile/water 0-95% gradient)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-54fc8814aea2487f9c2aef7c769bac18
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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