Acetic Acid → HCID 22100877, compound

Participants

Reaction Steps

A dry flask containing 67 mg (0.113 mmol) of 2-[2-(3,5-dimethylphenyl)-3-[2-[methyl-[4-(pyridin-4-yl)butyl]amino]ethyl]-1H-indol-5-yl]-N,N-dibutylisobutyramide (prepared according to EXAMPLE 7.2), 33.9 mg (1.3 mmol) of paraformaldehyde, and 100 mg of powdered 3A molecular sieves was fitted with a septum and purged thoroughly with N2. Next, 2.65 mL of MeOH and 65.2 μL (67.8 mg, 1.13 mmol) of glacial acetic acid were added, and the mixture was stirred at room temperature for 35 minutes. Then 28.4 mg (0.452 mmol) of sodium cyanoborohydride was added, followed after an additional 20 minutes by 2.5 mL of anhydrous THF. After a few minutes, TLC indicated complete reaction. Therefore, the mixture was filtered, and the filtrate was shaken in a separatory funnel with brine. The aqueous phase was extracted an additional 3 times with CH2Cl2. The combined organic fractions were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was flash chromatographed on silica gel (gradient elution with 99:1:0.1 to 95:5:0.5 CH2Cl2 -MeOH-concd. NH4OH) to yield 31.1 mg (45%) of the title compound as a glass; homogeneous by TLC in 95:5:0.5 CH2Cl2 -MeOH-concd. NH4OH. 500 MHz 1H NMR (CDCl3) was consistent with the assigned structure. m/e=609.5 (M+H).

Provenance & Evidence