تفاعل #49108

ord-2a827efff7e9408287c544a8c6786163

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    ترشيحThe mixture was filtered
  2. 2
    غسيلthe resin washed with DCM (2×4 ml)
  3. 3
    غسيلCombined organics were washed with saturated sodium hydrogen carbonate (20 ml)
  4. 4
    أخرىthe layers separated
  5. 5
    غسيلThe cartridge was washed with DCM (2 volumes), 50% methanol in DCM (1 volume) and methanol (2 volumes)
  6. 6
    غسيلElution
  7. 7
    أخرىwith 1M ammonia in methanol (2 volumes) and evaporation of the solvent
  8. 8
    أخرىafforded a colourless gum
  9. 9
    غسيلChromatography on silica gel (10 g) eluting with 0-100% ethyl acetate in pentane gradient

الإجراء التجريبي

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).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07745642B2uspto-grants-2010_06