Water → HCID 53311109, compound

HRID 1967025Notes

Reaction equation

HRID 1967025 reaction equation
C([O:3][C:4]([C:6]1[S:10][C:9]([NH:11][C:12](=[O:43])[C:13]2[CH:18]=[C:17]([Cl:19])[C:16]([O:20][C:21]3[CH:26]=[CH:25][N:24]=[CH:23][C:22]=3[C:27]([N:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[N:32]([CH:39]4[CH2:41][CH2:40]4)[CH2:31][CH2:30]3)=[O:28])=[CH:15][C:14]=2[Cl:42])=[N:8][C:7]=1[CH3:44])=[O:5])C.O.O.[OH-].[Li+]>O1CCOCC1>[Cl:42][C:14]1[CH:15]=[C:16]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[C:27]([N:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([CH:39]3[CH2:40][CH2:41]3)[CH2:31][CH2:30]2)=[O:28])[C:17]([Cl:19])=[CH:18][C:13]=1[C:12]([NH:11][C:9]1[S:10][C:6]([C:4]([OH:5])=[O:3])=[C:7]([CH3:44])[N:8]=1)=[O:43]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2×HCID 53311108HCID 53311108, compound

Product 1

HCID 53311109HCID 53311109, compoundYield 37.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 0.16 g (0.25 mmol) 2-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzoylamino}-4-methyl-thiazole-5-carboxylic acid ethyl ester (Example 45) in 2 mL dioxane were added 2 mL water and 0.013 g (0.31 mmol) lithiumhydroxide monohydrate. The resulting suspension was stirred at room temperature for 2 hours and then stirred at reflux temperature for 5.5 hours. Another 0.013 g (0.31 mmol) lithiumhydroxide monohydrate were added and heating was continued for another 8 hours. The oil bath was removed and the reaction mixture was stirred at room temperature overnight. After evaporation of the organic solvent the pH of the resulting solution was adjusted to 2 to 3 using 1M aqueous hydrochloric acid and the solution was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The product was purified by preparative HPLC (Phenomenex Gemini Column) with a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give 0.058 g (37%) of the title compound as a light brown solid. MS (ESI): m/z=624.1 [M+H]+.

Workup

  1. stirringstirred
  2. temperatureat reflux temperature for 5.5 hours
  3. temperatureheating
  4. waitwas continued for another 8 hours
  5. customThe oil bath was removed
  6. stirringthe reaction mixture was stirred at room temperature overnight
  7. customAfter evaporation of the organic solvent the pH of the resulting solution
  8. extractionthe solution was extracted three times with ethyl acetate
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe product was purified by preparative HPLC (Phenomenex Gemini Column) with a gradient of acetonitrile

Sources & evidence

ORD record
ord-5f596ba85c8e4f7f98db82ee4670975b
Source dataset
uspto-grants-2013_04
Patent number
US08420647B2

Reaction notes

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