Reaction #45870

Reaction equation

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

Yield 41.5%

Solvents

methanol

chloroform

chloroform

Conditions

Workup

1. 1
   ExtractionThe aqueous layer was extracted twice with chloroform
2. 2
   Washwashed with saturated brine
3. 3
   Dryingdried over anhydrous sodium sulfate
4. 4
   OtherThe insoluble matter was separated by filtration
5. 5
   Otherthe solvent was evaporated away
6. 6
   Otherthe resulting residue was purified by preparative TLC (eluent, chloroform

Procedure

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.

Source