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

HRID 1386111Notes

Reaction equation

HRID 1386111 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-2a9323a14ce1493389a2a731e84e7f64
Source dataset
uspto-grants-2001_07
Patent number
US06265419B1

Reaction notes

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