4-azidobenzaldehyde

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500-ml flask were placed 15 g of 2-methoxyacetophenone (made by Aldrich Co., 99% purity), 15 g of p-azidobenzaldehyde (manufactured by Kanto Chemical Co., Ltd.), 50 g of 10% aqueous solution of NaOH, and 50 g of methanol. The mixture was stirred in a yellow light at 25° C. for 24 hours. After completion of the reaction, the deposited crystals were filtered, washed with water, dried, and recrystallized from ethanol. In a 500-ml flask were placed After completion of the reaction the deposited crystals were filtered washed with water dried recrystallized from ethanol

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500-ml flask were placed 15 g of 2-methoxyacetophenone (made by Aldrich Co., 99% purity), 15 g of p-azidobenzaldehyde (manufactured by Kanto Chemical Co., Ltd.), 50 g of 10% aqueous solution of NaOH, and 50 g of methanol. The mixture was stirred in a yellow light at 25° C. for 24 hours. After completion of the reaction, the deposited crystals were filtered, washed with water, dried, and recrystallized from ethanol. In a 500-ml flask were placed After completion of the reaction the deposited crystals were filtered washed with water dried recrystallized from ethanol

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

Procedure: 4-Azidobenzaldehyde (14.71 g, 0.1 mol) was dissolved in a solvent mixture of isopropyl alcohol (50 g) and pure water (15 g). Under cooling in an ice bath, sodium hydroxide (1 g) dissolved in pure water (10 g) was added to the solution, and the resultant mixture was stirred for ten minutes. Acetaldehyde (4.41 g, 0.1 mol) was added to the mixture, and the resultant mixture was stirred for two hours at the same temperature. Subsequently, acetaldehyde (4.41 g, 0.1 mol) was again added to the mixture, and the resultant mixture was stirred for a further three hours. The formed precipitates were collected through filtration and dried, to thereby yield 4.82 g of p-azido-cinnamaldehyde as brown solid (yield: 28%) as a mixture containing acetaldehyde (2.7%). Under cooling in an ice bath was added to the solution The formed precipitates were collected through filtration dried

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

Procedure: 4-Azidobenzaldehyde (29.42 g, 0.2 mol) and propionaldehyde (12.22 g, 0.2 mol) were dissolved in a solvent mixture of isopropyl alcohol (100 g) and pure water (50 g). Under cooling in an ice bath, sodium hydroxide (2 g) dissolved in pure water (20 g) was added to the solution, and the mixture was stirred for two hours. Propionaldehyde (12.22 g, 0.2 mol) was added again to the mixture, and the resultant mixture was stirred for a further three hours. The formed precipitates were collected through filtration and dried, to thereby yield 23.14 g of p-azido-2-methylcinnamaldehyde as yellow crystals (yield: 62%). The compound thus obtained was identified on the basis of the 1H-NMR measurements shown in Table 1. Under cooling in an ice bath was added to the solution The formed precipitates were collected through filtration dried

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

Procedure: To a 500-mL round bottom flask with stirbar was added 4-amino-benzaldehyde (2.0 g, 0.0165 mol) and diluted hydrochloric acid (4 N, 150 mL). The mixture was cooled in ice-water bath to keep the temperature around 0° C. Sodium nitrite (2.28 g, 0.033 mol) solution in water (20 mL) was added to the above mixture at 0° C. and stirred for 0.5 h, and then sodium azide (2.15 g, 0.033 mol) solution in water (20 mL) was added to the above mixture dropwise to keep the temperature at 0° C. (a lot of foam were formed in this process). The reaction was warmed gradually to room temperature over 1 h, and then permitted to react at room temperature overnight. TLC showed that there was only one main product in the reaction mixture so the reaction was stopped. The crude product was extracted with EtOAc (50 mL×5) and the combined organic layers were dried with anhydrous MgSO4. After removing the solvent, a light yellow liquid was obtained as the pure final product (2.30 g, 95% yield). IR (neat): 3062, 2114, 1693, 1597, 1578, 1503, 1282, 1166, 1126, 852 cm−1. 1H NMR (400 MHz, CDCl3): δ 9.97 (s, 1H), 7.91 (dt, J=8.8, 2.0 Hz, 2H), 7.19 (dt, J=8.8, 2.0 Hz, 2H); 1H NMR (400 MHz, MeOD): δ 7.45 (dt, J=8.8, 2.0 Hz, 2H), 7.08 (dt, J=8.8, 2.0 Hz, 2H), 5.38 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 190.7, 146.4, 133.2, 131.6, 119.5. the temperature around 0° C at 0° C. were formed in this process) to react at room temperature overnight The crude product was extracted with EtOAc (50 mL×5) the combined organic layers were dried with anhydrous MgSO4 After removing the solvent

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

Procedure: To a 500-mL round bottom flask with stirbar was added 4-amino-benzaldehyde (2.0 g, 0.0165 mol) and diluted hydrochloric acid (4 N, 150 mL). The mixture was cooled in ice-water bath to keep the temperature around 0° C. Sodium nitrite (2.28 g, 0.033 mol) solution in water (20 mL) was added to the above mixture at 0° C. and stirred for 0.5 h, and then sodium azide (2.15 g, 0.033 mol) solution in water (20 mL) was added to the above mixture dropwise to keep the temperature at 0° C. (a lot of foam were formed in this process). The reaction was warmed gradually to room temperature over 1 h, and then permitted to react at room temperature overnight. TLC showed that there was only one main product in the reaction mixture so the reaction was stopped. The crude product was extracted with EtOAc (50 mL×5) and the combined organic layers were dried with anhydrous MgSO4. After removing the solvent, a light yellow liquid was obtained as the pure final product (2.30 g, 95% yield), IR (neat): 3062, 2114, 1693, 1597, 1578, 1503, 1282, 1166, 1126, 852 cm−1. 1H NMR (400 MHz, CDCl3): δ 9.97 (s, 1H), 7.91 (dt, J=8.8, 2.0 Hz, 2H), 7.19 (dt, J=8.8, 2.0 Hz, 2H); 1H NMR (400 MHz, MeOD): δ 7.45 (dt, J=8.8, 2.0 Hz, 2H), 7.08 (dt, J=8.8, 2.0 Hz, 2H), 5.38 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 190.7, 146.4, 133.2, 131.6, 119.5. the temperature around 0° C at 0° C. were formed in this process) to react at room temperature overnight The crude product was extracted with EtOAc (50 mL×5) the combined organic layers were dried with anhydrous MgSO4 After removing the solvent

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

Procedure: 3-Ethynyl-5-methyl-1H-indazole (1.0 g; 6.4 mmol; 1.0 eq.) and 4-azidobenzaldehyde (prepared as described in Chem. Med. Chem. (2009), 4(7), 1182-1188; 1.30 g; 7.04 mmol; 1.1 eq.) were dissolved in 1,4-dioxane (15 mL). D-(−)-isoascorbic acid sodium salt (127 mg; 0.64 mmol; 0.10 eq.) followed by a solution of copper sulfate pentahydrate (32 mg; 0.13 mmol; 0.02 eq.) in water (1.5 mL) were added and the reaction mixture was stirred at 90° C. for 3.5 hours. To complete the reaction more D-(−)-isoascorbic acid sodium salt (127 mg; 0.64 mmol; 0.10 eq.) and copper sulfate pentahydrate (32 mg; 0.13 mmol; 0.02 eq.) were added again and the reaction mixture was heated at 10° C. for 8 h. 1,4-dioxane was removed under reduced pressure an the residue was sonicated in a mixture of EtOAc and water (1:1). The resulting solid was filtered and dried to afford the title compound as a beige solid (1.94 g, 100%). 1H NMR (300 MHz, DMSO-d6) δ: 13.29 (brs, 1H), 10.11 (s, 1H), 9.46 (s, 1H), 8.34 (d, J=8.6 Hz, 2H), 8.18 (d, J=8.6 Hz, 2H), 8.14 (m, 1H), 7.51 (d, J=8.4 Hz, 1H), 7.28 (dd, J=8.4 Hz, 1.4 Hz, 1H), 2.49 (s, 3H). were added were added again the reaction mixture was heated at 10° C. for 8 h 1,4-dioxane was removed under reduced pressure an the residue was sonicated in a mixture of EtOAc and water (1:1) The resulting solid was filtered dried

Conditions: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 g 4-fluoro benzaldehyde and 50 g sodium azide were dispersed in 150 ml dry dimethyl sulfoxide. Subsequently, the mixture was heated for 3 hours at 105° C. while nitrogen was introduced. The mixture was poured into 200 ml water, and the solution extracted with 200 ml dichloro methane (three times). Then the solvent was distilled off by means of a vacuum rotation vaporizer. 53 g of a liquid remained having infrared (IR) and nuclear magnetic resonance (NMR) spectra consistent with the 4-azido benzaldehyde structure. was introduced the solution extracted with 200 ml dichloro methane (three times) Then the solvent was distilled off by means of a vacuum rotation vaporizer

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

Procedure: In 100 ml of ethanol were dissolved 10 g of 4-methoxycyclohexanone and 30 g of para-azidobenzaldehyde, after which a solution of 1 g of sodium hydroxide in 1 ml of water was added, and the resulting mixture was subjected to reaction in a brown flask at room temperature for 2 days. The crystals formed were separated by suction filtration, washed with ethanol, and then recrystallized from methyl Cellosolve to obtain 4.7 g of yellow crystals having a decomposition point of 145° to 150° C. (differential thermal analysis, the rate of heating: 5° C./min). the resulting mixture was subjected to reaction in a brown flask at room temperature for 2 days The crystals formed were separated by suction filtration washed with ethanol recrystallized from methyl Cellosolve

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500-ml flask were placed 15 g of 2-methoxyacetophenone (made by Aldrich Co., 99% purity), 15 g of p-azidobenzaldehyde (manufactured by Kanto Chemical Co., Ltd.), 50 g of 10% aqueous solution of NaOH, and 50 g of methanol. The mixture was stirred in a yellow light at 25° C. for 24 hours. After completion of the reaction, the deposited crystals were filtered, washed with water, dried, and recrystallized from ethanol. In a 500-ml flask were placed After completion of the reaction the deposited crystals were filtered washed with water dried recrystallized from ethanol