ACH-806 synthesis

Yield:-

Reaction Conditions:

in dichloromethane;acetone at 20;

Steps:

4.2

A solution of ammonium thiocyanate (4.5 g, 60 mmol) in acetone (25 ml) is added to a suspension of nicotinyl chloride hydrochloride (3.6 g, 20 mmol) in acetone (50 ml). The reaction is stirred for 1 h at room temperature followed by the addition of a solution of 4-pentyloxy-3-trifluoromethyl aniline (4.9 g, 20 mmol) in methylene chloride (25 ml). Stirring is continued over night at room temperature. The solvent is evaporated and the residue suspended in water (100 ml) and extracted with ethylacetate (3×75 ml). The organic extract is washed successively with 10% aq. NaHCO₃ solution (×1), water, and brine. The organic layer is dried over sodium sulphate and evaporated. The residue is crystallized from methanol to give the desired product 1H NMR (300 MHz, CDCl₃): δ 12.34 (s, 1H), 9.35 (s, 1H), 9.16 (s, 1H), 8.91-8.88 (d, 1H, J=6.4 Hz), 8.23-8.20 (t, 1H, J=2.2 Hz), 7.85-7.81 (d, 1H, J=12 Hz), 7.54-7.50 (q, 2H, J=4.8 Hz), 7.04 (d, 1H, J=8.7, 1.0 Hz), 4.10-4.06 (t, 2H, J=6.3 Hz), 1.92-1.83 (m, 2H), 1.50-1.42 (m, 4H), 0.97-0.93 (m, 3H). MS (APCI) m/z 412.14 [M+H]⁺.

References:

US2006/25416,2006,A1 Location in patent:Page/Page column 32