Diisopropylethylamine → 3-cyano-N-[(2S)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide

Participants

Reaction Steps

3-Cyano-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-1-carboxamide (see Method 19; 2.38 g, 6.3 mmol) and 4-azetidin-3-ylmorpholine dihydrochloride (see WO 00/63168; 1.49 g, 6.9 mmol) were mixed together with CH2Cl2 (120 mL) and DIPEA (1.63 g, 12.6 mmol). The mixture was stirred until all the chemicals were dissolved. Sodium triacetoxyborohydride (1.87 g, 8.8 mmol) was added and the solution was stirred at room temperature overnight. The solvent was removed and the residue was partitioned between ethyl acetate and saturated NaHCO3 (aq). The phases were separated and the aqueous solution was extracted with ethyl acetate. The combined organic solutions were dried over MgSO4 and the solvent was removed by evaporation. The residue was diluted with a small amount of acetonitrile and the solution was kept in a freezer overnight. The crystals were collected by filtration and more material was then obtained from the mother liquor by an additional crystallisation from acetonitrile. There was obtained 1.43 g (45%) in total of the title compound as an off-white solid. 1H NMR (500 MHz, CD3OD): 1.4-4.2 (cm, 31H), 7.0-7.6 (cm, 6H); LCMS: m/z 505 (M+1)+.

Provenance & Evidence