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

HRID 327387Notes

Reaction equation

HRID 327387 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([CH2:33][CH:34]2[CH:39]([NH2:40])[CH:38]3[CH2:41][CH2:42][N:35]2[CH2:36][CH2:37]3)[CH2:32][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:40][CH:39]1[CH:38]2[CH2:37][CH2:36][N:35]([CH2:42][CH2:41]2)[CH:34]1[CH2:33][N:27]1[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1)=[O:9]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 116942165-Chloro-2-methoxy-4-(methylamino)benzoic acidHCID 191084162-(1-Piperidylmethyl)-1-azabicyclo[2.2.2]octan-3-amine

Product 1

HCID 98022695-Chloro-2-methoxy-4-(methylamino)-N-[2-(1-piperidinyl-methyl)-1-azabicyclo[2.2.2]oct-3-yl]benzamideYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 5-chloro-2-methoxy-4-(methylamino)-benzoic acid (1.95 g, 9.0 mmoles) in anhydrous tetrahydrofuran (10 ml) was treated with 1,1'-carbonyldiimidazole (1.49 g, 9.2 mmoles), stirred at room temperature for 90 minutes, then added to a cooled (0° C.) solution of 2-(1-piperidylmethyl)-1-azabicyclo[2.2.2]octan-3-amine (2.12 g, 9.5 mmoles) in anhydrous tetrahydrofuran (10 ml) under nitrogen. After 18 hours at room temperature the solution was concentrated in vacuo and partitioned between methylene chloride (100 ml) and 1.0N sodium hydroxide (40 ml). The organic solution was separated and washed with 1.0N sodium hydroxide (40 ml), saturated aqueous sodium bicarbonate (40 ml), and brine (40 ml), dried (Na2SO4), and concentrated in vacuo. Filtration through alumina (eluted with 15% methanol/ethyl acetate) provided 3.24 g (86%) of a colorless foam.

Workup

  1. additionadded to
  2. concentrationAfter 18 hours at room temperature the solution was concentrated in vacuo
  3. custompartitioned between methylene chloride (100 ml) and 1.0N sodium hydroxide (40 ml)
  4. customThe organic solution was separated
  5. washwashed with 1.0N sodium hydroxide (40 ml), saturated aqueous sodium bicarbonate (40 ml), and brine (40 ml)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. filtrationFiltration through alumina (eluted with 15% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-f4aa843298184aa585394698f9d79ee3
Source dataset
uspto-grants-1993_12
Patent number
US05273972

Reaction notes

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