1,1'-Carbonyldiimidazole → 5-Chloro-N-[2-(di-n-propylaminomethyl)-1-azabicyclo[2.2.2]oct-3-yl]-2-methoxy-4-(methylamino)benzamide

HRID 327390Notes

Reaction equation

HRID 327390 reaction equation
[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:27]([N:30]([CH2:34][CH:35]1[CH:40]([NH2:41])[CH:39]2[CH2:42][CH2:43][N:36]1[CH2:37][CH2:38]2)[CH2:31][CH2:32][CH3:33])[CH2:28][CH3:29]>O1CCCC1>[Cl:1][C:2]1[C:3]([NH:13][CH3:14])=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([NH:41][CH:40]1[CH:39]2[CH2:42][CH2:43][N:36]([CH2:37][CH2:38]2)[CH:35]1[CH2:34][N:30]([CH2:31][CH2:32][CH3:33])[CH2:27][CH2:28][CH3:29])=[O:9]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 116942165-Chloro-2-methoxy-4-(methylamino)benzoic acidHCID 541147442-(Di-n-propylaminomethyl)-1-azabicyclo[2.2.2]-octan-3-amine

Product 1

HCID 191084175-Chloro-N-[2-(di-n-propylaminomethyl)-1-azabicyclo[2.2.2]oct-3-yl]-2-methoxy-4-(methylamino)benzamideYield 79.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.35 g, 15.5 mmoles) in anhydrous tetrahydrofuran (20 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.56 g, 15.8 mmoles), and stirred for one hour at room temperature. Nitrogen was bubbled through the solution for 20 minutes, and a solution of 2-(di-n-propylaminomethyl)-1-azabicyclo[2.2.2]-octan-3-amine (3.95 g, 15.8 mmoles) in tetrahydrofuran (10 ml) was added dropwise. The mixture was maintained at room temperature for 18 hours, and at 50° C. for 1 hour, then concentrated in vacuo. The residue was partitioned between methylene chloride and 1.0N aqueous sodium carbonate, and the organic layer was separated. The aqueous solution was extracted with methylene chloride, and the combined organic solution was dried (Na2SO4) and concentrated in vacuo. The residue was filtered through alumina (eluted with 3% methanol/methylene chloride) to provide 5.38 g (79%) of a colorless foam.

Workup

  1. customNitrogen was bubbled through the solution for 20 minutes
  2. temperatureThe mixture was maintained at room temperature for 18 hours
  3. waitat 50° C. for 1 hour
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between methylene chloride and 1.0N aqueous sodium carbonate
  6. customthe organic layer was separated
  7. extractionThe aqueous solution was extracted with methylene chloride
  8. dry with materialthe combined organic solution was dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. filtrationThe residue was filtered through alumina (eluted with 3% methanol/methylene chloride)

Sources & evidence

ORD record
ord-b9d45ae7d0834e58b77961b360d5871d
Source dataset
uspto-grants-1993_12
Patent number
US05273972

Reaction notes

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