4-(dibutylamino)benzaldehyde

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

Procedure: The title compound was prepared from p-nitrophenylacetic acid (9.92 g, 0.055 mol) and 4-dibutylamino-benzaldehyde (14.32 g, 0.055 mol) in piperidine (5 mL) using the procedure described in Example 1, Step A. This procedure yielded a red solid, 4.12 g (0.012 mol, 16%) of the desired product.

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

Procedure: The title compound was prepared from p-nitrophenylacetic acid (9.92 g, 0.055 mol) and 4-dibutylamino-benzaldehyde (14.32 g, 0.055 mol) in piperidine (5 mL) using the procedure described in Example 1, Step A. This procedure yielded a red solid, 4.12 g (0.012 mol, 16%) of the desired product.

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 5.00 g (21 mmol) of 4-dibutylaminobenzaldehyde, 4.27 g (24 mmol) of 4-nitrophenylacetic acid, 1.80 g (21 mmol) of piperidine, and 50 mL of xylenes was heated with stirring at reflux of 20 hours with continuous removal of water using a Dean-Stark apparatus. The mixture turned dark red. Approximately half the xylenes was distilled, 20 mL of heptane was added, and the residue was cooled to -30° C. Red crystals separated which were collected and then recrystallized from toluene/heptane. Yield: 2.81 g (37%), mp 117-119 (lit2 182°-182.5° C.). was heated Approximately half the xylenes was distilled 20 mL of heptane was added Red crystals separated which were collected recrystallized from toluene/heptane Yield: 2.81 g (37%), mp 117-119 (lit2 182°-182.5° C.)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20 ml sample of N,N-dimethylformamide (DMF) was cooled to 0° C. for 1 hour and at 25° C. for 1 hour, then N,N-dibutylaniline was added slowly. The reaction mixture was heated at 90° C. for 16 hours, then cooled and poured onto 50 g of ice. A brown oil separated which was taken up in dichloromethane. The extract was washed with saturated aqueous bicarbonate then with water containing a little ammonium chloride, dried (MgSO4), and the solvent was removed at reduced pressure. The brown, oily residue was distilled in vacuo to product 6.65 g (58%) of a yellow liquid. cooled A brown oil separated which The extract was washed with saturated aqueous bicarbonate with water containing a little ammonium chloride, dried (MgSO4) the solvent was removed at reduced pressure The brown, oily residue was distilled in vacuo to product 6.65 g (58%) of a yellow liquid

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20 ml sample of N,N-dimethylformamide (DMF) was cooled to 0° C. for 1 hour and at 25° C. for 1 hour, then N,N-dibutylaniline was added slowly. The reaction mixture was heated at 90° C. for 16 hours, then cooled and poured onto 50 g of ice. A brown oil separated which was taken up in dichloromethane. The extract was washed with saturated aqueous bicarbonate then with water containing a little ammonium chloride, dried (MgSO4), and the solvent was removed at reduced pressure. The brown, oily residue was distilled in vacuo to product 6.65 g (58%) of a yellow liquid. cooled A brown oil separated which The extract was washed with saturated aqueous bicarbonate with water containing a little ammonium chloride, dried (MgSO4) the solvent was removed at reduced pressure The brown, oily residue was distilled in vacuo to product 6.65 g (58%) of a yellow liquid

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

Procedure: Prepared by Procedure F and Scheme R using 4-(dibutylamino)benzaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 464.6 (M+H)+. Prepared by Procedure F and Scheme R

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

Procedure: Prepared by Procedure F and Scheme R using 4-(dibutylamino)benzaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 464.6 (M+H)+. Prepared by Procedure F and Scheme R

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

Procedure: To a dry vial was added the salt 6 (708 mg, 2 mmol), 4-dibutylaminobenzaldehyde (467 mg, 2 mmol) and the vial was purged with N2. Ethanol (10 ml) was added via syringe, followed by piperidine (1 ml). Within 5 minutes the color began changing to deep red. The mixture was stirred at room temperature for 12 hours, concentrated and the salt was precipitated with dry ether. Following solvent removal, the salt was again dissolved in EtOH (8 ml) and precipitated with ether. The resulting fluorophore was filtered under a nitrogen atmosphere and dried. Yield: 1.04 g (91%). MS (dual ESI+): 204.69186 (M+H+)2+ HRMS calc. 409.3457. H-NMR (DMSO-D6): 0.92 (t, J=12 Hz, 6H); 1.38 (m, 4H); 1.48 (m, 4H); 2.24 (m, 2H); 3.22l-3.35 (m, 11 H); 3.85 (t, J=9 Hz, 4H); 4.25 (t, J=12 Hz, 2H); 6.8 (d, J=8 Hz, 2H); 6.97 (s, 2H); 7.75 (d, J=8 Hz, 2H); 8.05 (d, J=6 Hz, 2H); 8.95 (d, J=6 Hz, 2H). the vial was purged with N2 Ethanol (10 ml) was added via syringe concentrated the salt was precipitated with dry ether Following solvent removal the salt was again dissolved in EtOH (8 ml) precipitated with ether The resulting fluorophore was filtered under a nitrogen atmosphere dried

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

Procedure: In a stream of argon, to 40 ml of tetrahydrofuran was added 8.0 g of phenyllithium (19% solution in dibutylether) (18.1 mmol). To this mixture, 3.81 g (8.2 mmol) of 4-(hydroxymethyl)benzyltriphenylphosphonium bromide was added under cooling. After the mixture was stirred at the same temperature, 2.0 g (8.6 mmol) of 4-(dibutylamino)benzaldehyde was added thereto. The mixture was stirred at the same temperature for 1 hour. After the reaction mixture was added to water, extraction with toluene, washing with a saturated saline solution, and drying over anhydrous sodium sulfate were performed. Toluene was evaporated off. The residue was purified by silica gel column chromatography to give 2.37 g of a yellow liquid (yield: 85.5%). under cooling was added washing with a saturated saline solution drying over anhydrous sodium sulfate Toluene was evaporated off The residue was purified by silica gel column chromatography

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

Procedure: In a stream of argon, to 70 ml of tetrahydrofuran was added 10.45 g of phenyllithium (19% solution in dibutylether) (23.6 mmol), and 8.09 g (20.5 mmol) of 2-thenyl triphenylphosphonium chloride was added thereto under cooling. To this mixture was added dropwise 4.92 g (21.0 mmol) of 4-(dibutylamino)benzaldehyde. The mixture was stirred at the same temperature for 1 hour. After the reaction mixture was poured into water, extraction with toluene, washing with a saturated saline solution, drying over anhydrous sodium sulfate, and concentration were performed. The residue was purified by silica gel column chromatography to give an orange liquid. This liquid was dissolved in 200 ml of toluene and 200 mg of iodine was added thereto. After stirred at room temperature for 15 minutes, the mixture was added to water and the phases were separated. The organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give 6.09 g of an orange oily matter (yield: 94.8%). was added under cooling washing with a saturated saline solution drying over anhydrous sodium sulfate, and concentration The residue was purified by silica gel column chromatography to give an orange liquid After stirred at room temperature for 15 minutes the phases were separated The organic layer was dried over anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography to give 6.09 g of an orange oily matter (yield: 94.8%)

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

Procedure: A mixture of 23.3 g (0.10 mol) of 4-dibutylaminobenzaldehyde, 17 g (0.10 mol) of di(methylsulfonyl)methane, 15 mL of pyridine, 7 drops of piperidine, and 400 mL of benzene was heated at reflux for 18 hr, with continuous azeotropic separation of the water evolved. Approximately half of the benzene was removed by distillation, and 200 mL of heptane was added. Upon cooling to room temperature, a white precipitate formed. The crude product was purified by silica gel chromatography followed by micrystallization from ethanol, from toluene, and from methanol, producing 18 g (46%) of (2). A sample of (2) that was sublimed in vacuo melted at 114.5°-115° C. was heated Approximately half of the benzene was removed by distillation, and 200 mL of heptane was added a white precipitate formed The crude product was purified by silica gel chromatography

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

Procedure: The title compound was prepared from p-nitrophenylacetic acid (9.92 g, 0.055 mol) and 4-dibutylamino-benzaldehyde (14.32 g, 0.055 mol) in piperidine (5 mL) using the procedure described in Example 1, Step A. This procedure yielded a red solid, 4.12 g (0.012 mol, 16%) of the desired product.