Lithium Hydroxide → HCID 59416116, compound

HRID 2061805Notes

Reaction equation

HRID 2061805 reaction equation
[CH2:1]([NH:3][C:4](=[O:46])[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]([CH:22]([CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH2:23][OH:24])[CH:17]=[C:16]([C:31]([O:33]CC)=[O:32])[C:15]3=[O:36])=[C:8]([C:37]2[S:38][CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[N:41]=2)[CH:7]=1)[CH3:2].[OH-].[Li+]>O1CCCC1.CO.O>[CH2:1]([NH:3][C:4](=[O:46])[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]([CH:22]([CH:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH2:23][OH:24])[CH:17]=[C:16]([C:31]([OH:33])=[O:32])[C:15]3=[O:36])=[C:8]([C:37]2[S:38][CH:39]=[C:40]([C:42]([F:45])([F:43])[F:44])[N:41]=2)[CH:7]=1)[CH3:2]

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 59415925HCID 59415925, compound

Product 1

HCID 59416116HCID 59416116, compoundYield 26.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-yl)-1-(2-hydroxy-1-(tetrahydro-2H-pyran-4-yl)ethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (Example 103, 107 mg, 0.16 mmol, 1 equiv.) in tetrahydrofuran (1 mL) and methanol (1 mL) was added 2 M lithium hydroxide (0.162 mL, 0.32 mmol). The reaction mixture was heated to 100° C. for 15 min in a microwave. The reaction mixture was cooled to room temperature and diluted with water. The reaction mixture was filtered, and the filtrate was dried. Purification via reverse phase HPLC (C18, acetonitrile/water 0-95% gradient) and concentrated under reduced pressure to provide 6-(6-(3-ethylureido)-4-(4-(trifluoromethyl)thiazol--yl)pyridin-3-yl)-1-(2-hydroxy-1-(tetrahydro-2H-pyran-4-yl)ethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid as a light yellow solid (26.5 mg, 26%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationThe reaction mixture was filtered
  3. customthe filtrate was dried
  4. customPurification via reverse phase HPLC (C18, acetonitrile/water 0-95% gradient)
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b15d9b66b0d1452fbf84a777ac7d10de
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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