1,1'-Carbonyldiimidazole → 4-Amino-N-(1-azabicyclo[3.2.1]oct-5-ylmethyl)-5-chloro-2-methoxybenzamide

A suspension of 4-amino-5-chloro-2-methoxybenzoic acid (1.72 g, 8.5 mmol) in anhydrous tetrahydrofuan (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.

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)

ORD record

ord-40169b770c9f42239cde7e0d4cb368b9

Source dataset

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05244907