Reaktion #58500

Reaktionsgleichung

sodium triacetoxyborohydride

2,4,6-trifluoro-N-[6-(piperidin-4-ylcarbonyl)pyridin-2-yl]benzamide

cyclopropylmethanal

dichloromethane

acetic acid

→

title compound

Ausbeute 77.0%

2,4,6-Trifluoro-N-[6-(1-cyclopropylmethyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide dihydrochloride salt

Ausbeute 77.0%

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 3 hrs
2. 2
   WaschenWash the column with methanol
3. 3
   Waschenelute with 2M ammonia/methanol
4. 4
   Einengenconcentrate the eluent
5. 5
   SonstigePurify the residue by flash chromatography
6. 6
   Wascheneluting with 10% ammonia/methanol in dichloromethane

Vorschrift

Combine 2,4,6-trifluoro-N-[6-(piperidin-4-ylcarbonyl)pyridin-2-yl]benzamide (0.05 g, 0.138 mmol), cyclopropylmethanal (0.10 g, 1.38 mmol) and dichloromethane (5 mL), and stir at ambient temperature. After 15 minutes, add glacial acetic acid (0.02 mL, 0.35 mmol) followed by sodium-triacetoxyborohydride (0.038 g, 0.18 mmol) with stirring. After 3 hrs., dilute the reaction mixture with methanol (5 mL) and load on an SCX column (10 g). Wash the column with methanol, elute with 2M ammonia/methanol, and concentrate the eluent. Purify the residue by flash chromatography, eluting with 10% ammonia/methanol in dichloromethane, to obtain the free base of the title compound (0.045 g, 77%). Dissolve the free base in dichloromethane (5 mL), treat with 1M hydrogen chloride in diethylether (0.25 mL), and concentrate the mixture to obtain the dihydrochloride salt. M.p.=140° C.; HRMS: Obs. m/z 418.1743; Calc. m/z 418.1742; 1H NMR (CDCl3): 11.51 (bs, 1H), 10.34 (bs, 1H), 8.38 (m, 1H), 8.11 (m, 1H), 7.78(d, 1H), 7.42 (m, 2H), 3.79 (m, 1H), 3.64 (m, 2H), 2.98 (m, 4H), 2.17 (m, 2H), 1.99 (m, 2H), 1.13 (m, 1H), 0.65 (m, 2H), 0.39 (m, 2H).

Quelle