Acetic Acid → (S)-4-Chloro-N-cyclopentyl-N-(3-methyl-1-(pyrrolidin-1-yl)butan-2-yl)benzamide

Cyclopent-3-enone (57.9 mg, 0.70 mmol) was added to a mixture of (S)-3-methyl-1-(pyrrolidin-1-yl)butan-2-amine (109 mg, 0.70 mmol), which is commercially available, in THF (1.7 mL). After 10 min was a solution of sodium cyanoborohydride (58 mg, 0.92 mmol) in THF (0.9 mL) added. The resultant mixture was stirred at rt for 3 h. Acetic acid (0.3 mL, 5.24 mmol) and MeOH (2 mL) was added and the mixture stirred at rt overnight. The reaction mixture was concentrated and the residue dissolved in DMF (2.5 mL). DIPEA (0.5 mL, 2.86 mmol) and a solution of 4-chlorobenzoyl chloride (2.2 mL, 1.01 mmol) in DCM (2 mL) was added. The resultant mixture was stirred at rt overnight. H2O (0.5 mL) and MeOH (5 mL) were added and the mixture was stirred for 10 min. The solvent was removed under reduced pressure and the residue mixed in NaOH (1 N aq., 10 mL). The water layer was extracted with DCM (3×10 mL) and the combined organic layer were washed with brine (10 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (17 mg, 7%).

1. concentrationThe reaction mixture was concentrated
2. dissolutionthe residue dissolved in DMF (2.5 mL)
3. stirringthe mixture was stirred for 10 min
4. customThe solvent was removed under reduced pressure
5. additionthe residue mixed in NaOH (1 N aq., 10 mL)
6. extractionThe water layer was extracted with DCM (3×10 mL)
7. washthe combined organic layer were washed with brine (10 mL)
8. filtrationfiltered through a phase separator
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by preparative HPLC

ORD record

ord-5b5c6bec9bfe44aba60f1d0179af14a3

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08361998B2