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

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 297 grams of a mixture of 70% Indancarbaldehyde and 30% indan-2-carbaldehyde, 300 grams of ethylene glycol, 6 grams of p-toluenesulfonic acid and 300 grams of toluene are heated 2 hours at reflux using a Dean-Stark trap to separate water. The mixture is cooled and washed with 200 milliliters of a 5 weight % sodium carbonate solution. The organic layer is distilled to provide 321 grams of 2-indanyl-4-methyl-1,3-dioxolane (b.p.121° C. at 3 mm). at reflux to separate water The mixture is cooled washed with 200 milliliters of a 5 weight % sodium carbonate solution The organic layer is distilled

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

Procedure: A solution of 297 grams of a mixture of 70% Indancarbaldehyde and 30% indan-2-carbaldehyde, 300 grams of ethylene glycol, 6 grams of p-toluenesulfonic acid and 300 grams of toluene are heated 2 hours at reflux using a Dean-Stark trap to separate water. The mixture is cooled and washed with 200 milliliters of a 5 weight % sodium carbonate solution. The organic layer is distilled to provide 321 grams of 2-indanyl-4-methyl-1,3-dioxolane (b.p.121° C. at 3 mm). at reflux to separate water The mixture is cooled washed with 200 milliliters of a 5 weight % sodium carbonate solution The organic layer is distilled

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

Procedure: A solution of 297 grams of a mixture of 70% Indancarbaldehyde and 30% indan-2-carbaldehyde, 300 grams of ethylene glycol, 6 grams of p-toluenesulfonic acid and 300 grams of toluene are heated 2 hours at reflux using a Dean-Stark trap to separate water. The mixture is cooled and washed with 200 milliliters of a 5 weight % sodium carbonate solution. The organic layer is distilled to provide 321 grams of 2-indanyl-4-methyl-1,3-dioxolane (b.p.121° C. at 3 mm). at reflux to separate water The mixture is cooled washed with 200 milliliters of a 5 weight % sodium carbonate solution The organic layer is distilled

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: This compound was prepared from the hydrochloride salt of cis-4-(2,5-dimethyl-benzoimidazol-1-yl)-cyclohexylamine and indan-2-carbaldehyde. 1H-NMR is consistent with the assigned structure, LC-MS showed a single peak, C25H31N3 (m/e) calcd 373.2518, obsd 374.2 (M+H).

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

Procedure: This compound was prepared from the hydrochloride salt of cis-2-[1-(4-amino-cyclohexyl)-5-chloro-1H-benzoimidazol-2-yl]-propan-2-ol and indan-2-carbaldehyde. 1H-NMR is consistent with the assigned structure, LC-MS showed a single peak, C26H32ClN3O (m/e) calcd 437.2234, obsd 438.2 (M+H).

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

Procedure: A solution of 5-cyano-3-(3-pyridyl)-1-(4′-aminophenyl)pyrazole (185 mg, 0.7 mmol) and indane 2-carboxaldehyde (0.96 mmol, 140 mg) in methanol (9 mL) and acetic acid (1 mL) was stirred at room temp for 30 min. Sodium cyanoborohydride (124 mg, 2 mmol) was added and stirring continued at room temperature. After 3 h the solvent was evaporated under vacuum, and the residue was taken up in sodium bicarbonate solution (50 mL) and extracted with methylene chloride (3×50 mL). The combined extract was washed with water, dried over anhydrous sodium sulfate and evaporated. Chromatography of the residue over silica gel (eluant, 15% ethyl acetate in methylene chloride) gave the title compound as a cream colored solid, m.p. 156-158° C. 1H NMR (DMSO-d6): δ 2.68-2.82 (3H, m), 3.05-3.15 (4H, m), 6.36-6.42 (1H, br. t), 6.75-6.77 (2H, d, J=8.9 Hz), 7.09-7.15 (2H, m), 7.21-7.24 (4H, m), 7.45-7.47 (2H, d, J=8.8 Hz), 7.51-7.54 (1H, m), 7.98 (1H, s), 8.21-8.28 (1H, br. d.), 8.6-8.62 (1H, br. d.), 9.1 (1H, d, J=1.9 Hz). continued at room temperature After 3 h the solvent was evaporated under vacuum extracted with methylene chloride (3×50 mL) The combined extract was washed with water dried over anhydrous sodium sulfate evaporated

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

Procedure: A solution of 3-(3-pyridyl)-5-ethyl-1-(4′-aminophenyl)pyrazole (185 mg, 0.7 mmol) and indane 2-carboxaldehyde (0.96 mmol, 140 mg) in methanol (9 mL) and acetic acid (1 mL) was stirred at room temperature for 30 min. Sodium cyanoborohydride (124 mg, 2 mmol) was added and stirring continued at room temperature. After 3 h the solvent was evaporated under vacuum, the residue was taken up in sodium bicarbonate solution (50 mL), and extracted with methylene chloride (3×50 mL). The combined organic extracts were washed with water, dried over anhydrous sodium sulfate, and evaporated. Chromatography of the residue over silica gel (eluant, 35% ethyl acetate in methylene chloride) gave the title compound which was taken up in 50% aqueous acetonitrile containing 1% trifluoroacetic acid and lyophilized to give a light yellow solid. 1H NMR (DMSO-d6) δ 1.2 (3H, t, J=7.5 Hz), 2.63 (2H, q, J=7.5 Hz), 2.7-2.76 (3H, m), 3.05-3.12 (4H, m), 6.71 (2H, d, J=8.7 Hz), 6.98 (1H, s), 7.12-7.14 (2H, m), 7.21-7.24 (4H, m), 7.84-7.88 (1H, m), 8.65 (1H, br, d, J=8.2 Hz), 8.71 (1H, d, J=5.1 ),9.2 (1H, s). continued at room temperature After 3 h the solvent was evaporated under vacuum extracted with methylene chloride (3×50 mL) The combined organic extracts were washed with water dried over anhydrous sodium sulfate evaporated

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

Procedure: To a stirred ice-cold solution of the above amide (400 mg, 1.9 mmol) in ether (20 mL), was added lithium aluminium hydride (1 M in THF, 4 mL). After stirring the ice-cold mixture for 1 h, excess reducing agent was quenched by the careful addition of 1N sulfuric acid (10 mL). The reaction mixture was stirred for 5min, the ether layer was decanted and the remaining solid was washed with ether (100 mL). The combined ether extract was washed with water, dried over anhydrous sodium.sulfate, and evaporated to give indane 2-carboxaldehyde as a light brownish oil which was used without further purification in the next step. was quenched by the careful addition of 1N sulfuric acid (10 mL) the ether layer was decanted the remaining solid was washed with ether (100 mL) The combined ether extract was washed with water dried over anhydrous sodium sulfate, and evaporated