Methanol → 3,4-Dihydro-4-propyl-2H-1,2,4-benzothiadiazine-3-carboxylic acid 1,1-dioxide

HRID 617777Notes

Reaction equation

HRID 617777 reaction equation
C[O:2][CH:3]([O:8]C)[C:4](OC)=O.CO.[CH2:12]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([NH2:25])(=[O:24])=[O:23])[CH2:13][CH3:14].[OH-].[Na+]>O.O1CCOCC1>[CH2:12]([N:15]1[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[S:22](=[O:24])(=[O:23])[NH:25][CH:4]1[C:3]([OH:8])=[O:2])[CH2:13][CH3:14]

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 66647Acetic acid, 2,2-dimethoxy-, methyl esterHCID 218497762-(Propylamino)benzenesulfonamide

Product 1

HCID 543318053,4-Dihydro-4-propyl-2H-1,2,4-benzothiadiazine-3-carboxylic acid 1,1-dioxideYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

This compound was prepared according to the method of Close et. al., J. Org. Chem., 1961, 26, 3423-3433, incorporated by reference herein in its entirety. Thus, a solution of methyl dimethoxyacetate (3.6 g, 27.3 mmol) in water (50 l) was refluxed for 2.5 hours. A stillhead was attached and the methanol so generated was allowed to distill off (a total of 10 ml of liquid was collected, of which 5 ml was replenished with water). To the hot solution was added 2-(propylamino)benzenesulfonamide (4.5 g, 21.0 mmol) (prepared according to the procedure of Biressi et. al., Farmeco. Ed. Sci. (It.), 1969, 24, 199-220, incorporated by reference herein in its entirety) and 1,4-dioxane (5 ml, to give a homogeneous solution) and reflux was continued for 1.5 hours. The mixture was adjusted to pH 3 (2N NaOH), extracted with ethyl acetate and the organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated to give 4.8 g crude product which was recrystallized (ethyl acetate/hexanes) to give 2.5 g (44%) of the title compound as a white solid; NMR (DMSO-d6) δ 0.85 (t, J=7 Hz, 3H), 1.47-1.57 (m, 2H), 2.94-3.04 (m, 1H), 3.38 (br, 1H), 3.40-3.46 (m, 1H), 5.27 (d, J=6 Hz, 1H), 6.70 (t, J=7 Hz, 1H), 6.84 (d, J=7 Hz, 1H), 7.36 (t, J=7 Hz), 7.43 (d, J=7 Hz, 1H), 8.44 (d, J=7 Hz, 1H), 13.04 (br, 1H); MS: 269 m/z (M-H)- ; Anal. Calc'd for C11H14N2O4S: C, 48.88; H, 5.23; N, 10.37; S, 11.84; Found: C, 49.17; H, 5.21; N, 10.27; S, 11.54.

Workup

  1. customThis compound was prepared
  2. customof Close et. al., J
  3. distillationto distill off (a total of 10 ml of liquid
  4. customwas collected, of which 5 ml
  5. customprepared
  6. customto give a homogeneous solution) and
  7. temperaturereflux
  8. extractionextracted with ethyl acetate
  9. washthe organic phase was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give 4.8 g crude product which
  14. customwas recrystallized (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-144cc472774642bcb5c787fa87261500
Source dataset
uspto-grants-1999_09
Patent number
US05952328

Reaction notes

Loading…