Ammonia → 8'-{[(2S)-2-(Methoxymethyl)pyrrolidinyl]sulfonyl}-3',4'-dihydrospiro(1,3-dioxane-2,10' (2'H)-pyrimido(1,2-a)indole)

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[5′-{[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]sulfonyl}-2′-oxospiro[1,3-dioxane-2,3′-indol]-1′ (2′H)-yl]propanenitrile (4.48 g, 10.3 mmol), and wet Raney nickel (4.1 g) in 2M EtOH.NH3 (100 mL) and THF (100 mL) was hydrogenated in a Parr Hydrogenation Bottle (2L) at 45 lb/in2 hydrogen for 24 hours. The Raney nickel was removed by filtration through Sulka Floc. The filtrate was poured into a steel pressure vessel and heated to 135° C. for 51 hours. The reaction was cooled and the solvents were removed. The residue was taken up in CH2Cl2 and combined with silica gel. The solvent was removed and the adsorbate was flash chromatographed (Biotage KP silica gel, and step gradient of CH2Cl2/CH3OH/NH4OH (98.5/1.0/0.5-98/01.5/0.5)) to give the title compound as a white solid (0.63 g, 14.5% yield). Anal: Calc'd. for C20H27N3O5S: C, 56.99; H, 6.46; N, 9.97; Found: C, 56.80, H, 6.45, N, 9.87; NMR (400 MHz, DMSO-d6): consistent. MS: (ES+) m/z 422 [M+H]. Opt. Rotation: 94.1(calculated) at 25° C. in CH3OH (1% concentration), wavelength 589; m.p. 129-130°.

Provenance & Evidence