Potassium Carbonate → 9-[4-(Cyclobutyloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1622682Notes

Reaction equation

HRID 1622682 reaction equation
[O:1]=[S:2]1(=[O:19])[CH2:7][CH2:6][N:5]2[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=3)[C:4]2=[N:3]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:27]1[CH2:30][CH2:29][CH2:28]1.[OH-].[Na+]>CS(C)=O.C1COCC1.C(OCC)(=O)C>[CH:27]1([O:18][C:15]2[CH:16]=[CH:17][C:12]([C:11]3[C:4]4=[N:3][S:2](=[O:1])(=[O:19])[CH2:7][CH2:6][N:5]4[CH:8]=[CH:9][CH:10]=3)=[CH:13][CH:14]=2)[CH2:30][CH2:29][CH2:28]1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 78110Bromocyclobutane2×HCID 667478174-(2,2-Dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol

Product 1

HCID 667485219-[4-(Cyclobutyloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 20%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-(2,2-dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol (300 mg), potassium carbonate (390 mg) and bromocyclobutane (191 mg) in DMSO (5 mL) was stirred at 130° C. for 1 hr. Bromocyclobutane (100 mg) was added, and the mixture was stirred at room temperature overnight. 0.5N Aqueous sodium hydroxide solution, ethyl acetate and THF were added and the mixture was extracted. The extract was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was separated by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA containing system)). To the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was crystallized from acetonitrile, THF and diisopropyl ether to give the title compound (71.9 mg) as a white solid.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractionthe mixture was extracted
  3. washThe extract was washed with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was separated by HPLC (C18, mobile phase: water/acetonitrile (0.1% TFA containing system))
  7. additionTo the obtained fraction was added a saturated aqueous sodium hydrogen carbonate solution
  8. extractionthe mixture was extracted with ethyl acetate
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was crystallized from acetonitrile, THF and diisopropyl ether

Sources & evidence

ORD record
ord-505e7516341e484ab319ab355d4f7e3a
Source dataset
uspto-grants-2014_07
Patent number
US08778934B2

Reaction notes

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