反应详情

A mixture of 3′-[(2-chloroethyl)oxy]-4-biphenylcarboxamide and 3′-[(2-bromoethyl)oxy]-4-biphenylcarboxamide (Example II-1) (0.15 g), 4,4-dimethylcyclohexylamine hydrochloride (0.13 g, 0.8 mmol) (prepared according to J. Med. Chem. 1971, 14, p. 600-614) and triethylamine (0.14 g, 1.35 mmol) in methanol (2 mL) was placed in a microwave at 160° C. until the reaction was complete as monitored by LC/MS. The reaction mixture was poured into ethyl acetate and washed several times with 5% Na2CO3 (aq). Silica gel was added to the organic phase and the mixture was concentrated in vacuo. The residue was purified by silica gel chromatography. The fractions containing the desired product were combined and concentrated in vacuo. Dissolved the residue in ethanol, added 1.0N HCl in Et2O until acidic, added ethyl ether until turbid and let stand at room temperature. The resulting solid was filtered, washed with ethyl ether and dried to give 3′-({2-[(4,4-dimethylcyclohexyl)amino]ethyl}oxy)-4-biphenylcarboxamide hydrochloride as an off-white solid. (M+H) 367, 1.83 min. (LC/MS method A)

1. customwas placed in a microwave at 160° C. until the reaction
2. washwashed several times with 5% Na2CO3 (aq)
3. additionSilica gel was added to the organic phase
4. concentrationthe mixture was concentrated in vacuo
5. customThe residue was purified by silica gel chromatography
6. additionThe fractions containing the desired product
7. concentrationconcentrated in vacuo
8. dissolutionDissolved the residue in ethanol
9. additionadded 1.0N HCl in Et2O until acidic,
10. additionadded ethyl ether until turbid
11. customlet stand at room temperature
12. filtrationThe resulting solid was filtered
13. washwashed with ethyl ether
14. customdried