5-chloro-2-piperidin-1-ylaniline

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:

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

Procedure: Isonicotinoyl chloride hydrochloride (350 mg, 1.96 mmol, commercially available product), triethylamine (740 μl, 5.30 mmol), and a catalytic amount of 4-(dimethylamino)pyridine were sequentially added at room temperature to a dichloromethane (10 ml) solution of 5-chloro-2-(1-piperidinyl)aniline (378 mg, 1.79 mmol), obtained as described in Referential Example 15-2. The resulting mixture was stirred for 19 hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate=1/1). Thus, N-[5-chloro-2-(1-piperidinyl)phenyl]isonicotinamide (GIF-0341) (180 mg, 31.8%) was yielded as a colorless solid. obtained the resulting mixture was extracted three times with ethyl acetate The obtained organic layer was washed with a saturated sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate=1/1)

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

Procedure: Concentrated hydrochloric acid (2.00 ml, 24.0 mmol) and anhydrous tin dichloride (1.84 g, 9.70 mmol) were sequentially added at 0° C. to a methanol (10 ml) solution of 1-(4-chloro-2-nitrophenyl)piperidine (471 mg, 1.95 mmol), obtained as described in Referential Example 15-1. The resulting mixture was warmed to room temperature and stirred for 16 hours. A saturated aqueous solution of sodium bicarbonate was added to the mixture. The mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate=9/1). Thus, 5-chloro-2-(1-piperidinyl)aniline (388 mg, 94.3%) was yielded as a colorless oily material. obtained The mixture was extracted three times with ethyl acetate The obtained organic layer was washed with a saturated sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate=9/1)

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

Procedure: Isonicotinoyl chloride hydrochloride (350 mg, 1.96 mmol, commercially available product), triethylamine (740 μl, 5.30 mmol), and a catalytic amount of 4-(dimethylamino)pyridine were sequentially added at room temperature to a dichloromethane (10 ml) solution of 5-chloro-2-(1-piperidinyl)aniline (378 mg, 1.79 mmol), obtained as described in Referential Example 15-2. The resulting mixture was stirred for 19 hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate=1/1). Thus, N-[5-chloro-2-(1-piperidinyl)phenyl]isonicotinamide (GIF-0341) (180 mg, 31.8%) was yielded as a colorless solid. obtained the resulting mixture was extracted three times with ethyl acetate The obtained organic layer was washed with a saturated sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate=1/1)

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

Procedure: Concentrated hydrochloric acid (2.00 ml, 24.0 mmol) and anhydrous tin dichloride (1.84 g, 9.70 mmol) were sequentially added at 0° C. to a methanol (10 ml) solution of 1-(4-chloro-2-nitrophenyl)piperidine (471 mg, 1.95 mmol), obtained as described in Referential Example 15-1. The resulting mixture was warmed to room temperature and stirred for 16 hours. A saturated aqueous solution of sodium bicarbonate was added to the mixture. The mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate=9/1). Thus, 5-chloro-2-(1-piperidinyl)aniline (388 mg, 94.3%) was yielded as a colorless oily material. obtained The mixture was extracted three times with ethyl acetate The obtained organic layer was washed with a saturated sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate=9/1)

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

Procedure: Isonicotinoyl chloride hydrochloride (350 mg, 1.96 mmol, commercially available product), triethylamine (740 μl, 5.30 mmol), and a catalytic amount of 4-(dimethylamino)pyridine were sequentially added at room temperature to a dichloromethane (10 ml) solution of 5-chloro-2-(1-piperidinyl)aniline (378 mg, 1.79 mmol), obtained as described in Referential Example 15-2. The resulting mixture was stirred for 19 hours. Water was added to the mixture, and the resulting mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate=1/1). Thus, N-[5-chloro-2-(1-piperidinyl)phenyl]isonicotinamide (GIF-0341) (180 mg, 31.8%) was yielded as a colorless solid. obtained the resulting mixture was extracted three times with ethyl acetate The obtained organic layer was washed with a saturated sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (200 g, hexane/ethyl acetate=1/1)

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

Procedure: Concentrated hydrochloric acid (2.00 ml, 24.0 mmol) and anhydrous tin dichloride (1.84 g, 9.70 mmol) were sequentially added at 0° C. to a methanol (10 ml) solution of 1-(4-chloro-2-nitrophenyl)piperidine (471 mg, 1.95 mmol), obtained as described in Referential Example 15-1. The resulting mixture was warmed to room temperature and stirred for 16 hours. A saturated aqueous solution of sodium bicarbonate was added to the mixture. The mixture was extracted three times with ethyl acetate. The obtained organic layer was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate=9/1). Thus, 5-chloro-2-(1-piperidinyl)aniline (388 mg, 94.3%) was yielded as a colorless oily material. obtained The mixture was extracted three times with ethyl acetate The obtained organic layer was washed with a saturated sodium chloride solution dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The residue was purified by silica gel column chromatography (30 g, hexane/ethyl acetate=9/1)