Hydrochloric Acid → HCID 59617710, compound

HRID 2061806Notes

Reaction equation

HRID 2061806 reaction equation
[CH2:1]([NH:3][C:4](=[O:44])[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]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:23][OH:24])[CH:17]=[C:16]([C:29]([O:31]CC)=[O:30])[C:15]3=[O:34])=[C:8]([C:35]2[S:36][CH:37]=[C:38]([C:40]([F:43])([F:42])[F:41])[N:39]=2)[CH:7]=1)[CH3:2].[OH-].[Li+].Cl>O1CCCC1.CO.O>[CH2:1]([NH:3][C:4](=[O:44])[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]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:23][OH:24])[CH:17]=[C:16]([C:29]([OH:31])=[O:30])[C:15]3=[O:34])=[C:8]([C:35]2[S:36][CH:37]=[C:38]([C:40]([F:41])([F:43])[F:42])[N:39]=2)[CH:7]=1)[CH3:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 70835133HCID 70835133, compound

Product 1

HCID 59617710HCID 59617710, compoundYield 35.2%

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-hydroxy-3,3-dimethylbutan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Example 104, 212.7 mg, 0.34 mmol) in tetrahydrofuran (1 mL) and methanol (1 mL) was added 2 M lithium hydroxide (0.253 mL, 0.51 mmol). The reaction mixture was heated at 100° C. for 15 min in a microwave reactor. The reaction mixture was cooled to room temperature and diluted with water. 1 N HCl was added until pH 3-4 was reached. The precipitate that formed was collected by filtration, washed with water and hexanes. Purification via column chromatography (silica, 95:5 methylene chloride/methanol) provided (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxy-3,3-dimethylbutan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (72.3 mg, 35%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe precipitate that formed
  3. filtrationwas collected by filtration
  4. washwashed with water and hexanes
  5. customPurification via column chromatography (silica, 95:5 methylene chloride/methanol)

Sources & evidence

ORD record
ord-912ef4da46d14c339751c52250219833
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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