4-Amino-5-chloro-2-methoxybenzoic acid → 4-Amino-N-(1-azabicyclo[3.2.1]oct-5-ylmethyl)-5-chloro-2-methoxybenzamide

HRID 1612742Notes

Reaction equation

HRID 1612742 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH3:13])[CH:3]=1.[N:14]12[CH2:21][C:18]([CH2:22][NH2:23])([CH2:19][CH2:20]1)[CH2:17][CH2:16][CH2:15]2>O1CCCC1>[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([NH:23][CH2:22][C:18]23[CH2:21][N:14]([CH2:20][CH2:19]2)[CH2:15][CH2:16][CH2:17]3)=[O:8])=[C:4]([O:12][CH3:13])[CH:3]=1

Participants

4

Reactant 2

HCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 19795979{1-Azabicyclo[3.2.1]octan-5-yl}methanamine

Product 1

HCID 197959744-Amino-N-(1-azabicyclo[3.2.1]oct-5-ylmethyl)-5-chloro-2-methoxybenzamideYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 4-amino-5-chloro-2-methoxybenzoic acid (1.72 g, 8.5 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1-carbonyldiimidazole (1.46 g, 9.0 mmol), stirred for one hour, then degassed under a stream of nitrogen for 10 minutes. A solution of 1-azabicyclo[3.2.1]octane-5-methanamine (1.27 g, 9.0 mmol) in anhydrous tetrahydrofuran (8 mL) was added, and stirring was continued at room temperature for 18 hours and at 50° C. for one hour. The mixture was concentrated in vacuo and partitioned between toluene (100 mL) containing a little 2-propanol and saturated sodium carbonate (50 mL). The organic layer was separated and the organic solution was dried (Na2SO4). concentrated in vacuo, and triturated from cold ether. Recrystallization from acetonitrile (2 crops) afforded 1.92 g (70%) of colorless crystals; mp 185°-187° C.

Workup

  1. customdegassed under a stream of nitrogen for 10 minutes
  2. stirringstirring
  3. waitwas continued at room temperature for 18 hours and at 50° C. for one hour
  4. concentrationThe mixture was concentrated in vacuo
  5. custompartitioned between toluene (100 mL)
  6. additioncontaining a little 2-propanol and saturated sodium carbonate (50 mL)
  7. customThe organic layer was separated
  8. dry with materialthe organic solution was dried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customtriturated from cold ether
  11. customRecrystallization from acetonitrile (2 crops)

Sources & evidence

ORD record
ord-82841f9b0a42402184e04df30190a923
Source dataset
uspto-grants-1993_03
Patent number
US05190953

Reaction notes

Loading…