5-fluoro-2,3-dihydro-1H-inden-1-ol

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: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and 5-fluoro-2,3-dihydro-1H-inden-1-ol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.39-2.46 (1H, m), 2.59-2.64 (1H, m), 2.90-2.98 (1H, m), 3.13-3.20 (1H, m), 5.72-5.75 (1H, m), 5.84 (1H, d, J=1.6 Hz), 6.89-6.94 (1H, m), 6.98 (1H, d, J=8.8 Hz), 7.34-7.37 (2H, m), 7.62 (1H, d, J=1.6 Hz), 7.86 (1H, s), 8.64 (1H, d, J=4.8 Hz). [M+H] Calc'd for C18H13FN4O, 321; Found, 321.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Charged 5-fluoro-2,3-dihydroinden-1-one (486 mg, 3.22 mmol), methanol (8 mL) and dichloromethane (4 mL) to a flask, the mixture was cooled to 0° C. and NaBH4 (119 mg, 3.22 mmol) was added in portions. The reaction mixture was stirred at 0° C. for 15 min, warmed up to room temperature and stirred for 30 min. Added water, extracted with ethyl acetate twice, and washed the organic phase with brine and dried with anhydrous Na2SO4, concentrated to give the title compound (488 mg, 100%). 1H NMR (400 MHz, CDCl3): δ 1.94-2.02 (1H, m), 2.46-2.55 (1H, m), 2.76-7.84 (1H, m), 3.01-3.08 (1H, m), 5.20 (2H, t, J=5.6 Hz), 6.89-6.93 (2H, m), 7.32-7.36 (1H, m). warmed up to room temperature stirred for 30 min Added water, extracted with ethyl acetate twice washed the organic phase with brine dried with anhydrous Na2SO4 concentrated

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and 5-fluoro-2,3-dihydro-1H-inden-1-ol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.39-2.46 (1H, m), 2.59-2.64 (1H, m), 2.90-2.98 (1H, m), 3.13-3.20 (1H, m), 5.72-5.75 (1H, m), 5.84 (1H, d, J=1.6 Hz), 6.89-6.94 (1H, m), 6.98 (1H, d, J=8.8 Hz), 7.34-7.37 (2H, m), 7.62 (1H, d, J=1.6 Hz), 7.86 (1H, s), 8.64 (1H, d, J=4.8 Hz). [M+H] Calc'd for C18H13FN4O, 321. Found, 321.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Charged 5-fluoro-2,3-dihydroinden-1-one (486 mg, 3.22 mmol), methanol (8 mL) and dichloromethane (4 mL) to a flask, the mixture was cooled to 0° C. and NaBH4 (119 mg, 3.22 mmol) was added in portions. The reaction mixture was stirred at 0° C. for 15 min, warmed up to room temperature and stirred for 30 min. Added water, extracted with ethyl acetate twice, and washed the organic phase with brine and dried with anhydrous Na2SO4, concentrated to give the title compound (488 mg, 100%). 1H NMR (400 MHz, CDCl3): δ 1.94-2.02 (1H, m), 2.46-2.55 (1H, m), 2.76-7.84 (1H, m), 3.01-3.08 (1H, m), 5.20 (2H, t, J=5.6 Hz), 6.89-6.93 (2H, m), 7.32-7.36 (1H, m). warmed up to room temperature stirred for 30 min Added water, extracted with ethyl acetate twice washed the organic phase with brine dried with anhydrous Na2SO4 concentrated

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

Procedure: To a solution of 5-fluoro-indan-1-ol (0.293 g, 1.925 mmol) and methyl 4-imidazolecarboxylate (CAS#17325-26-7, 0.163 g, 1.290 mmol) in THF (10 mL) at 0° C. is added pMe2NPhP(Ph)2 (0.619 g, 1.925 mmol) and diisopropyl azodicarboxylate (94%, 0.414 g, 1.925 mmol). After 1 hour the mixture is warmed to room temperature and after 18 hours it is diluted with ethyl acetate and extracted with 1M aqueous HCl. The extracts are cooled to 0° C., and the pH is adjusted to ca. 9 with ice-cold 4M aqueous NaOH. The basic aqueous phase is extracted three times with dichloromethane, and the combined organic phases are dried over magnesium sulfate, filtered through a cotton plug, and concentrated. The resulting residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 1:0 to 99:1 to 49:1) to afford 3-(5-fluoro-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 261.0 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-(5-fluoro-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; 1H NMR (400 MHz, CDCl3) δ ppm 2.06-2.20 (m, 1 H), 2.71-2.85 (m, 1 H), 2.87-3.00 (m, 1 H), 3.00-3.14 (m, 1 H), 3.87 (s, 3 H), 6.47 (dd, J=7.7, 4.7 Hz, 1 H), 6.88-6.97 (m, 1 H), 7.01 (dd, J=8.6, 2.3 Hz, 1 H), 7.16 (dd, J=8.6, 5.1 Hz, 1 H), 7.19 (s, 1 H), 7.77 (s, 1 H). extracted with 1M aqueous HCl The extracts are cooled to 0° C. The basic aqueous phase is extracted three times with dichloromethane the combined organic phases are dried over magnesium sulfate filtered through a cotton plug concentrated The resulting residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 1:0 to 99:1 to 49:1)

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

Procedure: To a solution of 5-fluoroindanone (CAS#700-84-5, 0.942 g, 6.274 mmol) in methanol (15 mL) at 0° C. is added sodium borohydride (0.356 g, 9.411 mmol) in one portion. The cooling bath is removed and after 2 hours, the mixture is poured into water (100 mL) and the volatile organics are removed in vacuo. Extraction with dichloromethane, drying over magnesium sulfate, filtering through a cotton plug and concentration affords 5-fluoro-indan-1-ol, which is used in the next step without further purification. The cooling bath is removed and after 2 hours the mixture is poured into water (100 mL) the volatile organics are removed in vacuo Extraction with dichloromethane drying over magnesium sulfate filtering through a cotton plug and concentration

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and 5-fluoro-2,3-dihydro-1H-inden-1-ol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.39-2.46 (1H, m), 2.59-2.64 (1H, m), 2.90-2.98 (1H, m), 3.13-3.20 (1H, m), 5.72-5.75 (1H, m), 5.84 (1H, d, J=1.6 Hz), 6.89-6.94 (1H, m), 6.98 (1H, d, J=8.8 Hz), 7.34-7.37 (2H, m), 7.62 (1H, d, J=1.6 Hz), 7.86 (1H, s), 8.64 (1H, d, J=4.8 Hz). [M+H] Calc'd for C18H13FN4O, 321; Found, 321.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Charged 5-fluoro-2,3-dihydroinden-1-one (486 mg, 3.22 mmol), methanol (8 mL) and dichloromethane (4 mL) to a flask, the mixture was cooled to 0° C. and NaBH4 (119 mg, 3.22 mmol) was added in portions. The reaction mixture was stirred at 0° C. for 15 min, warmed up to room temperature and stirred for 30 min. Added water, extracted with ethyl acetate twice, and washed the organic phase with brine and dried with anhydrous Na2SO4, concentrated to give the title compound (488 mg, 100%). 1H NMR (400 MHz, CDCl3): δ 1.94-2.02 (1H, m), 2.46-2.55 (1H, m), 2.76-7.84 (1H, m), 3.01-3.08 (1H, m), 5.20 (2H, t, J=5.6 Hz), 6.89-6.93 (2H, m), 7.32-7.36 (1H, m). warmed up to room temperature stirred for 30 min Added water, extracted with ethyl acetate twice washed the organic phase with brine dried with anhydrous Na2SO4 concentrated

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

Procedure: The title compound was prepared from 2-(5-hydroxy-1H-pyrazol-1-yl)pyridine-4-carbonitrile and 5-fluoro-2,3-dihydro-1H-inden-1-ol according to the procedure for the preparation of Example 39, part C. 1H NMR (400 MHz, CDCl3): δ 2.39-2.46 (1H, m), 2.59-2.64 (1H, m), 2.90-2.98 (1H, m), 3.13-3.20 (1H, m), 5.72-5.75 (1H, m), 5.84 (1H, d, J=1.6 Hz), 6.89-6.94 (1H, m), 6.98 (1H, d, J=8.8 Hz), 7.34-7.37 (2H, m), 7.62 (1H, d, J=1.6 Hz), 7.86 (1H, s), 8.64 (1H, d, J=4.8 Hz). [M+H] Calc'd for C18H13FN4O, 321. Found, 321.