Reacción #45870

Ecuación de reacción

dimethylamine

acetic acid

sodium cyanoborohydride

sodium hydrogencarbonate

2-Cyclopropyl-5-methyl-7-(3-oxocyclopentyl)-6-phenyl-1,3-benzoxazole-4-carbonitrile

→

ammonia methanol

2-cyclopropyl-7-[(1R*,3R*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

Rendimiento 41.5%

Disolventes

methanol

chloroform

chloroform

Condiciones de reacción

Tratamiento posterior

1. 1
   ExtracciónThe aqueous layer was extracted twice with chloroform
2. 2
   Lavadowashed with saturated brine
3. 3
   Secadodried over anhydrous sodium sulfate
4. 4
   OtroThe insoluble matter was separated by filtration
5. 5
   Otrothe solvent was evaporated away
6. 6
   Otrothe resulting residue was purified by preparative TLC (eluent, chloroform

Procedimiento

2-Cyclopropyl-5-methyl-7-(3-oxocyclopentyl)-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-303) (44 mg, 0.12 mmol) was dissolved in chloroform (1 ml) and methanol (1 ml), and at 0° C., dimethylamine (2 M tetrahydrofuran solution) (247 μl, 0.49 mmol), acetic acid (29 μl, 0.49 mmol) and sodium cyanoborohydride (33 mg, 0.49 mmol) were added. The solution was gradually warmed up to room temperature, then stirred for 21 hours, and fractionated with chloroform and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was extracted twice with chloroform. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away and the resulting residue was purified by preparative TLC (eluent, chloroform:7 N ammonia/methanol solution=97:3, v/v) to obtain 2-cyclopropyl-7-[(1R*,3R*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (#141) (9.6 mg, 20%) as a white solid. Next, 2-cyclopropyl-7-[(1R*,3S*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (#142) (26 mg, 55%) was obtained as a white solid.

Fuente