Reacción #1896242

Ecuación de reacción

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester

Triethylamine

HATU

2-phenylpiperidine

→

title compound

Rendimiento 51.1%

(2-Phenyl-piperidin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)methanone

Rendimiento 51.1%

Disolventes

trifluoroacetic acid

DCM

acetonitrile

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe mixture was purified by HPLC
2. 2
   Lavadoeluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes
3. 3
   workup.ADDITIONThe fractions containing the desired product
4. 4
   Concentraciónwere concentrated under vacuum
5. 5
   Otroto give an oil which
6. 6
   OtroThe solvent was evaporated
7. 7
   Otrothe residue was purified by flash chromatography on an SCX-2 cartridge
8. 8
   Lavadowashing with acetonitrile
9. 9
   Lavadomethanol and then eluting with 2 M ammonia in methanol
10. 10
    workup.ADDITIONThe fractions containing the desired product
11. 11
    Concentraciónwere concentrated under vacuum

Procedimiento

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester (0.1 g, 0.32 mmol) was dissolved in acetonitrile (2 mL). Triethylamine (0.96 mmol), HATU (0.35 mmol) and 2-phenylpiperidine (0.35 mmol) were added and the reaction stirred at room temperature for 5 hours. The mixture was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum to give an oil which was dissolved in trifluoroacetic acid (3 mL) and DCM (5 mL) and stirred for 3 hours. The solvent was evaporated and the residue was purified by flash chromatography on an SCX-2 cartridge, washing with acetonitrile, then methanol and then eluting with 2 M ammonia in methanol. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.058 g). LCMS m/z 355.18 [M+H]+ RT=6.59 min (Analytical Method 2). 1H NMR (400 MHz, CHCl3-d): δ 7.4 (m, 2H), 7.25 (m, 4H), 6.9 (s, 1H), 3.2 (d, 2H), 2.9 (m, 2H), 2.7 (m, 2H), 2.6 (m, 3H), 2.4 (d, 1H), 2.1-1.8 (m, 3H), 1.8-1.4 (m, 6H).

Fuente