Hydrochloric Acid → HCID 59416074, compound

HRID 2061807Notes

Reaction equation

HRID 2061807 reaction equation
[CH2:1]([NH:3][C:4](=[O:43])[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]([CH:25]([CH3:27])[CH3:26])[CH2:23][OH:24])[CH:17]=[C:16]([C:28]([O:30]CC)=[O:29])[C:15]3=[O:33])=[C:8]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:42])([F:41])[F:40])[N:38]=2)[CH:7]=1)[CH3:2].[OH-].[Li+].Cl>O1CCCC1.CO.O>[CH2:1]([NH:3][C:4](=[O:43])[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]([CH:25]([CH3:27])[CH3:26])[CH2:23][OH:24])[CH:17]=[C:16]([C:28]([OH:30])=[O:29])[C:15]3=[O:33])=[C:8]([C:34]2[S:35][CH:36]=[C:37]([C:39]([F:40])([F:42])[F:41])[N:38]=2)[CH:7]=1)[CH3:2]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59416087HCID 59416087, compound

Product 1

HCID 59416074HCID 59416074, compoundYield 72%

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-methylbutan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Example 110, 213 mg, 0.35 mmol) in tetrahydrofuran (1 mL) and methanol (1 mL) was added 2 M lithium hydroxide (0.259 mL, 0.52 mmol). The reaction mixture was heated at 100° C. for 15 min in a microwave reactor. The reaction mixture was cooled to room temperature, diluted with water, and treated with 1 N HCl until pH 3-4. The precipitate that formed was collected by filtration, washed with water and hexanes. Purification via reverse phase HPLC (C18, acetonitrile/water 0-95% gradient) provided (S)-6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(1-hydroxy-3-methylbutan-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (146.4 mg, 72%).

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 reverse phase HPLC (C18, acetonitrile/water 0-95% gradient)

Sources & evidence

ORD record
ord-cc3591664d0f46b9980757804d5c7510
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

Loading…