Dimethylformamide → 3-(3-Isopentylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.2]octane fumarate

HRID 976299Notes

Reaction equation

HRID 976299 reaction equation
Cl[C:2]1[C:6]([CH:7]2[CH:12]3[CH2:13][CH2:14][N:9]([CH2:10][CH2:11]3)[CH2:8]2)=[N:5][S:4][N:3]=1.[OH2:15].[SH2:16].[Na].[C:18](=[O:21])([O-:20])[O-].[K+].[K+].Br[CH2:25][CH2:26][CH:27]([CH3:29])[CH3:28].CN([CH:33]=[O:34])C>O>[C:33]([OH:34])(=[O:15])/[CH:13]=[CH:14]/[C:18]([OH:20])=[O:21].[CH2:25]([S:16][C:2]1[C:6]([CH:7]2[CH:12]3[CH2:13][CH2:14][N:9]([CH2:10][CH2:11]3)[CH2:8]2)=[N:5][S:4][N:3]=1)[CH2:26][CH:27]([CH3:29])[CH3:28]

Participants

7

Reactant 5

HCID 6228Dimethylformamide2×HCID 78911-Bromo-3-methylbutaneHCID 11430Potassium CarbonateHCID 99427073-Chloro-4-quinuclidin-3-yl-1,2,5-thiadiazole2×HCID 53442613Sodium hydrogen sulfide hydrate

Product 1

HCID 217086333-(3-Isopentylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.2]octane fumarate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 3-(3-chloro-1,2,5-thiadiazol-4-yl)-1-azabicyclo[2.2.2]octane (Compound 8) (420 mg, 1.83 mmol), sodiumhydrogen sulfide monohydrate (245 mg, 3.70 mmol) and potassium carbonate (780 mg, 5.64 mmol) in DMF (20 ml) was stirred at room temperature for 2 h. A solution of 1-bromo-3-methylbutane (420 mg, 2.75 mmol) in DMF (5 ml) was added, and the reaction mixture was stirred at room temperature for 3 h. Water (20 ml) was added and the mixture was extracted with ethyl acetate (3×100 ml). The combined extract was washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography (eluent: CH2Cl2 :MeOH:NH4OH (8:2:0.5%)) to give the free base of the desired product in 400 mg yield. Crystallization of the residue with fumaric acid from isopropanol/ether gave the title compound in 370 mg yield. (Compound 99). M.p. 130°-132° C.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×100 ml)
  2. extractionThe combined extract
  3. washwas washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography (eluent: CH2Cl2 :MeOH:NH4OH (8:2:0.5%))

Sources & evidence

ORD record
ord-e34cb0ba6ac24311921ef0830eb47f81
Source dataset
uspto-grants-1997_03
Patent number
US05612351

Reaction notes

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