Hydrochloric Acid → HCID 89963258, compound

HRID 337810Notes

Reaction equation

HRID 337810 reaction equation
[CH3:1][O:2][C:3]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:4]=1[CH2:5][N:6]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][N:34]=1)[S:7]([C:10]1[C:11]([F:32])=[CH:12][C:13]([O:20][C@H:21]2[CH2:25][CH2:24][CH2:23][C@@H:22]2[C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)=[C:14]([CH:19]=1)[C:15]([O:17]C)=O)(=[O:9])=[O:8].[OH-].[Na+].Cl.C[N:49]1CCOCC1.ClC(OCC(C)C)=O.O.N>C1COCC1>[CH3:1][O:2][C:3]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:4]=1[CH2:5][N:6]([C:33]1[CH:38]=[CH:37][N:36]=[CH:35][N:34]=1)[S:7]([C:10]1[C:11]([F:32])=[CH:12][C:13]([O:20][C@H:21]2[CH2:25][CH2:24][CH2:23][C@@H:22]2[C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)=[C:14]([CH:19]=1)[C:15]([NH2:49])=[O:17])(=[O:8])=[O:9]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 62365Isobutyl chloroformateHCID 12896473Azane;hydrateHCID 89962904HCID 89962904, compound

Product 1

HCID 89963258HCID 89963258, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the methyl 5-{[(2,4-dimethoxybenzyl)(pyrimidin-4-yl)amino]sulfonyl}-4-fluoro-2-{[(1S*,2R*)-2-(1-methyl-1H-pyrazol-5-yl)cyclopentyl]oxy}benzoate (83.3 mg, 0.133 mmol) prepared in Example 62b in THF (2.0 mL), a 5 M aqueous sodium hydroxide solution (2.0 mL) was added, and the reaction solution was stirred at room temperature for 15 hours. To the reaction solution, 1 M hydrochloric acid (10 mL) was added with cooling on ice, followed by extraction with ethyl acetate. The thus obtained organic layer was washed with saturated saline. The organic layer was dried over anhydrous sodium sulfate and vacuum concentrated, and THF (2.0 mL) was added to the obtained residue. To the reaction solution, 4-methylmorpholine (20.0 μL, 0.183 mmol) and isobutyl chloroformate (23.0 μL, 0.183 mmol) were added in that order with cooling on ice, and the mixture was stirred for 1 hour with cooling on ice. Then, 28% ammonia water (2.0 mL) was added thereto, and the mixture was stirred at room temperature for 12 hours. To the reaction solution, saturated saline was added, followed by extraction with ethyl acetate. The thus obtained organic layer was washed with saturated saline. The organic layer was dried over anhydrous sodium sulfate and vacuum concentrated, and the obtained residue was purified with silica gel chromatography (dichloromethane/methanol=85:15) to yield the title compound (64.2 mg, 86%) as a colorless amorphous solid.

Workup

  1. temperaturewith cooling on ice
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe thus obtained organic layer was washed with saturated saline
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate and vacuum
  5. concentrationconcentrated
  6. additionTHF (2.0 mL) was added to the obtained residue
  7. temperaturewith cooling on ice
  8. stirringthe mixture was stirred for 1 hour
  9. temperaturewith cooling on ice
  10. stirringthe mixture was stirred at room temperature for 12 hours
  11. additionTo the reaction solution, saturated saline was added
  12. extractionfollowed by extraction with ethyl acetate
  13. washThe thus obtained organic layer was washed with saturated saline
  14. dry with materialThe organic layer was dried over anhydrous sodium sulfate and vacuum
  15. concentrationconcentrated
  16. customthe obtained residue was purified with silica gel chromatography (dichloromethane/methanol=85:15)

Sources & evidence

ORD record
ord-04a6d4f279634f8bb858eed7391c40f1
Source dataset
uspto-grants-2014_11
Patent number
US08889741B2

Reaction notes

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