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

HRID 327389Notes

Reaction equation

HRID 327389 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.[N:27]1([CH2:32][CH:33]2[CH:38]([NH2:39])[CH:37]3[CH2:40][CH2:41][N:34]2[CH2:35][CH2:36]3)[CH2:31][CH2:30][CH2:29][CH2:28]1>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:39][CH:38]1[CH:37]2[CH2:36][CH2:35][N:34]([CH2:41][CH2:40]2)[CH:33]1[CH2:32][N:27]1[CH2:28][CH2:29][CH2:30][CH2:31]1)=[O:9]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 116942165-Chloro-2-methoxy-4-(methylamino)benzoic acidHCID 191084192-(1-Pyrrolidinylmethyl)-1-azabicyclo[2.2.2]octan-3-amine

Product 1

HCID 191083915-Chloro-2-methoxy-4-(methylamino)-N-[2-(1-pyrrolidinyl-methyl)-1-azabicyclo[2.2.2]oct-3-yl]benzamideYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

a suspension of 5-chloro-2-methoxy-4-(methylamino)benzoic acid (3.13 g, 14.5 mmoles) in anhydrous tetrahydrofuran (20 ml) under nitrogen was treated with 1,1'-carbonyldiimidazole (2.44 g, 15 mmoles), stirred for 90 minutes, cooled (0° C.), and treated with 2-(1-pyrrolidinylmethyl)-1-azabicyclo[2.2.2]octane-3-amine (3.14 g, 15.0 mmoles) in anhydrous tetrahydrofuran (10 ml). After 24 hours at room temperature and one hour at 60° C., the solution was concentrated in vacuo and partitioned between methylene chloride (100 ml) and 1.0N aqueous sodium carbonate (50 ml). The organic layer was separated and the aqueous solution was extracted with methylene chloride (40 ml). The combined organic solution was washed with brine (50 ml), dried (Na2SO4), concentrated in vacuo, dissolved in tetrahydrofuran, and filtered. The filtrate was passed through alumina (eluted with 15% methanol/ethyl acetate), and concentrated in vacuo to provide 3.71 g (63%) of a colorless foam.

Workup

  1. waitAfter 24 hours at room temperature
  2. concentrationone hour at 60° C., the solution was concentrated in vacuo
  3. custompartitioned between methylene chloride (100 ml) and 1.0N aqueous sodium carbonate (50 ml)
  4. customThe organic layer was separated
  5. extractionthe aqueous solution was extracted with methylene chloride (40 ml)
  6. washThe combined organic solution was washed with brine (50 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. dissolutiondissolved in tetrahydrofuran
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-da6d09817f4f4bf4864265213cab4897
Source dataset
uspto-grants-1993_12
Patent number
US05273972

Reaction notes

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