Dimethylformamide → 3-[1-[4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid

HRID 350277Notes

Reaction equation

HRID 350277 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:29]=[CH:28][C:8]([CH2:9][N:10]2[CH:14]=[C:13]([CH2:15][CH2:16][C:17]([O:19]CC)=[O:18])[C:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:11]2)=[CH:7][CH:6]=1.[S:30]1[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=2[NH:33][C:32](=[O:40])[CH2:31]1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[O:40]=[C:32]1[N:33]([CH2:2][CH2:3][O:4][C:5]2[CH:29]=[CH:28][C:8]([CH2:9][N:10]3[CH:14]=[C:13]([CH2:15][CH2:16][C:17]([OH:19])=[O:18])[C:12]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:11]3)=[CH:7][CH:6]=2)[C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[S:30][CH2:31]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 213964H-1,4-Benzothiazin-3-oneHCID 69421065ethyl 3-[1-[4-(2-bromoethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]propionate

Product 1

HCID 694238053-[1-[4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acidYield 69%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 3-[1-[4-(2-bromoethoxy)benzyl]-3-phenyl-1H-pyrazol-4-yl]propionate (883 mg), 2H-1,4-benzothiazin-3(4H)-one (320 mg), potassium carbonate (530 mg) and N,N-dimethylformamide (10 ml) was stirred at 80° C. for 8 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to obtain a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio). After a mixture of the resulting colorless oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml) was stirred at room temperature for 3 hours, 1N hydrochloric acid (5 ml) was added to the mixture, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated to obtain 3-[1-[4-[2-(3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl)ethoxy]benzyl]-3-phenyl-1H-pyrazol-4-yl]propionic acid (680 mg, yield: 69%) as a colorless amorphous substance.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed successively with dilute hydrochloric acid and saturated aqueous sodium chloride solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto obtain a colorless oily substance from the fraction
  6. washeluted with ethyl acetate-hexane (1:2, volume ratio)
  7. additionAfter a mixture of the resulting colorless oily substance, 1N aqueous sodium hydroxide solution (5 ml), tetrahydrofuran (5 ml) and ethanol (5 ml)
  8. stirringwas stirred at room temperature for 3 hours
  9. addition1N hydrochloric acid (5 ml) was added to the mixture
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe ethyl acetate layer was washed with a saturated aqueous sodium chloride solution
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-9096b2cf6c8b483294999862b2c27b37
Source dataset
uspto-grants-2007_02
Patent number
US07179823B1

Reaction notes

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