Dicyclohexylcarbodiimide → N-[[1-(Dimethylamino)cyclopentyl](phenyl)methyl]-2,3-dimethyl benzamide

A mixture of {1-[amino(phenyl)methyl]cyclopentyl}dimethylamine D3 enantiomer 2 (0.102 g, 0.47 mmol), 2,3-dimethylbenzoic acid (0.100 g, 0.67 mmol), 1-hydroxybenzotriazole hydrate (0.092 g, 0.6 mmol) and PS-DCC (0.63 g of 1.3 mmol/g loading, 0.82 mmol) in DCM (7 ml) was shaken for 20 h. The mixture was filtered and the resin washed with DCM (2×4 ml). Combined organics were washed with saturated sodium hydrogen carbonate (20 ml), the layers separated and the organic layer applied to a 2 g SCX cartridge. The cartridge was washed with DCM (2 volumes), 50% methanol in DCM (1 volume) and methanol (2 volumes). Elution with 1M ammonia in methanol (2 volumes) and evaporation of the solvent afforded a colourless gum. Chromatography on silica gel (10 g) eluting with 0-100% ethyl acetate in pentane gradient afforded the title compound as a colourless solid (0.14 g; 86%). 1H NMR (CDCl3) δ: 0.90-1.15 (1H, m), 1.20-1.38 (1H, m), 1.40-1.55 (2H, m), 1.60-1.75 (2H, m), 1.79-1.90 (2H, m), 2.22 (6H, s), 2.28 (6H, s), 5.15 (1H, d, J=6 Hz), 6.98 (1H, d, J=6 Hz), 7.10-7.15 (1H, m), 7.19-7.27 (3H, m), 7.29-7.35 (2H, m), 7.39-7.43 (2H, m). Mass spectrum (Electrospray LC/MS), ES+: Found 351 (MH+). C23H30N2O requires 350. Ret. time 1.90 min. The title product was converted to the corresponding hydrochloride salt (0.150 g).

1. filtrationThe mixture was filtered
2. washthe resin washed with DCM (2×4 ml)
3. washCombined organics were washed with saturated sodium hydrogen carbonate (20 ml)
4. customthe layers separated
5. washThe cartridge was washed with DCM (2 volumes), 50% methanol in DCM (1 volume) and methanol (2 volumes)
6. washElution
7. customwith 1M ammonia in methanol (2 volumes) and evaporation of the solvent
8. customafforded a colourless gum
9. washChromatography on silica gel (10 g) eluting with 0-100% ethyl acetate in pentane gradient

ORDレコード

ord-2a827efff7e9408287c544a8c6786163

出典データセット

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07745642B2