反应详情

To a solution of cis-(octahydro-quinolin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)-methanone (CC-033) (0.065 g, 0.20 mmol) in acetonitrile (1 mL) was added triethylamine (0.59 mmol), HATU (0.22 mmol) and N-t-butyloxycarbonyl β-alanine (0.22 mmol). The reaction mixture was stirred for 4 hours, and then the solvent was removed by evaporation. The residue was dissolved in TFA (2 mL) and DCM (2 mL) and the reaction mixture stirred for 2 hours. The solvent was evaporated and the residue purified by flash chromatography on an SCX-2 cartridge, eluting with acetonitrile and then 2 M ammonia in methanol. The fractions containing 3-amino-1-{4-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-propan-1-one were concentrated under vacuum to a colourless oil (0.089 g). The oil was dissolved in DCM (1 mL) and triethylamine (0.33 mmol) and methanesulphonyl chloride (0.22 mmol) were added. The mixture was stirred for 18 hours and then diluted with water and DCM. The organic solution was separated, dried and the solvent evaporated. The residue was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid). The fractions containing the desired product were concentrated under vacuum to give the title compound as a colourless oil (0.047 g). LCMS mk 482.09 [M+H]+ RT=9.52 min (Analytical Method 2).

1. customthe solvent was removed by evaporation
2. dissolutionThe residue was dissolved in TFA (2 mL)
3. stirringDCM (2 mL) and the reaction mixture stirred for 2 hours
4. customThe solvent was evaporated
5. customthe residue purified by flash chromatography on an SCX-2 cartridge
6. washeluting with acetonitrile
7. additionThe fractions containing 3-amino-1-{4-[4-(octahydro-quinoline-1-carbonyl)-thiophen-2-yl]-piperidin-1-yl}-propan-1-one
8. concentrationwere concentrated under vacuum to a colourless oil (0.089 g)
9. dissolutionThe oil was dissolved in DCM (1 mL)
10. stirringThe mixture was stirred for 18 hours
11. customThe organic solution was separated
12. customdried
13. customthe solvent evaporated
14. customThe residue was purified by HPLC
15. washeluting with 10%-98% acetonitrile in water (0.1% formic acid)
16. additionThe fractions containing the desired product
17. concentrationwere concentrated under vacuum