Methylhydrazine → 3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine

HRID 1818792Notes

Reaction equation

HRID 1818792 reaction equation
Br[CH2:2][CH2:3][CH:4]([N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[S:7]1(=[O:23])=[O:22])[CH3:5].C1(=O)[NH:28][C:27](=O)C2=CC=CC=C12.[K].CNN>CN(C)C=O.CCOC(C)=O>[F:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[N:8]1[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N:6]([CH:4]([CH3:5])[CH2:3][CH2:2][NH:28][CH3:27])[S:7]1(=[O:22])=[O:23]

Participants

6

Reactant 3

HCID 6061MethylhydrazineHCID 24194345Phthalimide potassium saltHCID 687098281-(3-Bromo-1-methylpropyl)-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide

Product 1

HCID 249378893-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amineYield 36.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-(3-bromo-1-methylpropyl)-3-(2-fluorophenyl)-1,3-dihydro-2,1,3-benzothiadiazole 2,2-dioxide (0.1 g, 0.25 mmol) was dissolved in dimethylformamide (2 mL) in a microwave cuvette and potassium phthalimide (0.06 g, 0.3 mmol) was added. The mixture was irradiated at 100° C. for 3 minutes. Upon cooling the mixture was diluted with EtOAc and washed with water and brine then dried with Na2SO4. Upon concentration, the residue was dissolved in MeOH (5 mL), methyl hydrazine (0.06 g, 1.25 mmol) was added and the mixture heated to reflux for 5 hours. Upon cooling the reaction was concentrated and water (10 ml) added followed by acetic acid (to pH 4). After 1 hour the mixture was filtered and basified to pH 14 with NaOH then extracted with dichloromethane. The organic extracts were washed with water, dried with Na2SO4 and purified via Isco chromatography (Redisep, silica, gradient 0-10% 7M ammonia/MeOH solution in dichloromethane) to afford 32 mg of 3-[3-(2-fluorophenyl)-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-N-methylbutan-1-amine.

Workup

  1. additionwas added
  2. customThe mixture was irradiated at 100° C. for 3 minutes
  3. temperatureUpon cooling the mixture
  4. washwashed with water and brine
  5. dry with materialthen dried with Na2SO4
  6. concentrationUpon concentration
  7. dissolutionthe residue was dissolved in MeOH (5 mL)
  8. temperaturethe mixture heated
  9. temperatureto reflux for 5 hours
  10. temperatureUpon cooling the reaction
  11. concentrationwas concentrated
  12. additionwater (10 ml) added
  13. filtrationAfter 1 hour the mixture was filtered
  14. extractionthen extracted with dichloromethane
  15. washThe organic extracts were washed with water
  16. dry with materialdried with Na2SO4
  17. custompurified via Isco chromatography (Redisep, silica, gradient 0-10% 7M ammonia/MeOH solution in dichloromethane)

Sources & evidence

ORD record
ord-f10189be1003470f9f9072d64e6705e1
Source dataset
uspto-grants-2009_10
Patent number
US07601722B2

Reaction notes

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