Reacción #5475

Ecuación de reacción

1-azabicyclo[3.3.1]nonane-5-methanamine

4-amino-5-chloro-2-(2-methoxyethoxy)benzoic acid

1,1'-carbonyldiimidazole

→

colorless crystals

Rendimiento 49.0%

4-Amino-N-(1-azabicyclo[3.3.1]non-5-ylmethyl)-5-chloro-2-(2-methoxyethoxy)benzamide

Rendimiento 49.0%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrodegassed under a stream of nitrogen over 10 minutes
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued at room temperature for 18 hours
4. 4
   ConcentraciónThe solution was concentrated in vacuo
5. 5
   Lavadowashed with saturated sodium carbonate (50 mL)
6. 6
   SecadoThe organic solution was dried (Na2SO4)
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   ConcentraciónThe filtrate was concentrated in vacuo and, at this point
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónthe filtrate was concentrated in vacuo
11. 11
    Otrotriturated from cold ether
12. 12
    Otrorecrystallized from acetonitrile (2 crops)

Procedimiento

A solution of 4-amino-5-chloro-2-(2-methoxyethoxy)benzoic acid (2.09 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, degassed under a stream of nitrogen over 10 minutes, and cooled (0° C.). A solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (1.36 g, 8.8 mmol) in tetrahydrofuran (5 mL) was added dropwise, and stirring was continued at room temperature for 18 hours. The solution was concentrated in vacuo and the residue was taken up in methylene chloride (100 mL) and washed with saturated sodium carbonate (50 mL). The organic solution was dried (Na2SO4), concentrated in vacuo, and passed through a short column of alumina (eluted with 5% methanol/methylene chloride). The filtrate was concentrated in vacuo and, at this point, appeared to be contaminated with some highly insoluble impurity. The residue was taken up in tetrahydrofuran and filtered, and the filtrate was concentrated in vacuo, triturated from cold ether, and recrystallized from acetonitrile (2 crops) to afford 1.59 g (49%) of colorless crystals; mp 154.0°-155.5° C.

Fuente