2,3-dihydro-1H-indene-2-carboxamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-|cis-2,6-Dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl|-indan-2-carboxylic acid amide. Thionyl chloride (42 μL, 0.577 mmol) was added to 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxyphenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid (250 mg, 0.502 mmol) in THF (4 mL) at 50 C for 1 h and then concentrated. The crude mixture was then dissolved in THF (4 mL) and ammonium hydroxide (300 μL) was added. The cloudy brown solution was stirred for an additional 3 h at room temperature. The solution was then concentrated and purified by silica gel column chromatography (0-20% MeOH in dichloromethane) to afford 4-[cis-2,6-dimethyl-4-(4-trifluoromethoxy-phenyl)-piperazine-1-sulfonyl]-indan-2-carboxylic acid amide (190 mg, 76%). 1H NMR (400 MHz, CD3OD) δ ppm. 7.71 (d, 1H), 7.47 (d, 1H), 7.34 (t, 1H), 7.10 (d, 2H), 6.94-6.91 (m, 2H), 4.20-4.14 (m, 1H), 4.05-3.90 (m, 1H), 3.54 (d, 2H), 3.41-3.21 (m, 5H), 2.77 (dd, 1H), 2.68 (dd, 1H), 1.51 (d, 3H), 1.49 (d, 3H). LCMS: 498.7 (M+1)+. concentrated The crude mixture was then dissolved in THF (4 mL) ammonium hydroxide (300 μL) was added The solution was then concentrated purified by silica gel column chromatography (0-20% MeOH in dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-indancarboxylic acid (1.4 g, 8.63 mmol) was dissolved in anhydrous DMF (20 mL), and the following was added sequentially: DIPEA (3.02 mL, 17.26 mmol), HATU (3.94 g, 10.36 mmol), and HMDS (2.17 mL, 10.36 mmol) after 30 min of stirring at rt. After stirring for 20 h at rt, the solution was taken up in EtOAc and washed with 0.5M HCl (3×), water (3×), and 10% aq. sodium carbonate (3×). The organic phase was collected and dried over magnesium sulfate, and concentrated in vacuo. The solid residue was recrystallized from EtOH to afford the title compound as sharp, colorless crystals. (Yield: 861 mg, 5.06 mmol, 59%) 1H NMR (400 MHz, CDCl3) 7.34-7.12, 5.52, 3.41-3.08 the following was added sequentially washed with 0.5M HCl (3×), water (3×), and 10% aq. sodium carbonate (3×) The organic phase was collected dried over magnesium sulfate concentrated in vacuo The solid residue was recrystallized from EtOH