5-chloro-1H-indole-2-carbaldehyde

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

Procedure: 5-Chloro-1H-indole-2-carbaldehyde (0.15 g, 0.76 mmol), NaCNBH3 (0.040 g, 0.63 mmol) and Et3N (0.088 mL, 0.63 mmol) was added to a stirred solution of 3-amino-1H-pyrrole-2-carboxylic acid ethyl ester hydrochloride (0.12 g, 0.63 mmol) in methanol (3 mL). The resulting mixture was stirred at r.t. overnight. The reaction mixture was heated to 50° C. Additional NaCNBH3 (0.5 equiv.) was added and the mixture was stirred at 50° C. for 3 h. A few drops of HOAc was added, and after 1 h the reaction mixture was cooled to r.t. and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (2 mL) and methanol (2 mL). Benzoyl isothiocyanate (0.093 mL, 0.69 mmol) was added and after stirring at r.t. for 1 h the mixture was concentrated in vacuo. The residue was dissolved in ammonia (7N in methanol, 3 mL) and heated at 80° C. for 2 h. The precipitated product was filtered and washed through with methanol and diethyl ether, followed by purification by preparative HPLC, obtaining 0.063 g (30%) of the title compound as a solid. The reaction mixture was heated to 50° C the mixture was stirred at 50° C. for 3 h after 1 h the reaction mixture was cooled to r.t. was concentrated in vacuo The residue was dissolved in CH2Cl2 (2 mL) after stirring at r.t. for 1 h the mixture was concentrated in vacuo The residue was dissolved in ammonia (7N in methanol, 3 mL) heated at 80° C. for 2 h The precipitated product was filtered washed through with methanol and diethyl ether followed by purification by preparative HPLC

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

Procedure: 5-Chloro-1H-indole-2-carbaldehyde (0.15 g, 0.76 mmol), NaCNBH3 (0.040 g, 0.63 mmol) and Et3N (0.088 mL, 0.63 mmol) was added to a stirred solution of 3-amino-1H-pyrrole-2-carboxylic acid ethyl ester hydrochloride (0.12 g, 0.63 mmol) in methanol (3 mL). The resulting mixture was stirred at r.t. overnight. The reaction mixture was heated to 50° C. Additional NaCNBH3 (0.5 equiv.) was added and the mixture was stirred at 50° C. for 3 h. A few drops of HOAc was added, and after 1 h the reaction mixture was cooled to r.t. and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (2 mL) and methanol (2 mL). Benzoyl isothiocyanate (0.093 mL, 0.69 mmol) was added and after stirring at r.t. for 1 h the mixture was concentrated in vacuo. The residue was dissolved in ammonia (7N in methanol, 3 mL) and heated at 80° C. for 2 h. The precipitated product was filtered and washed through with methanol and diethyl ether, followed by purification by preparative HPLC, obtaining 0.063 g (30%) of the title compound as a solid. The reaction mixture was heated to 50° C the mixture was stirred at 50° C. for 3 h after 1 h the reaction mixture was cooled to r.t. was concentrated in vacuo The residue was dissolved in CH2Cl2 (2 mL) after stirring at r.t. for 1 h the mixture was concentrated in vacuo The residue was dissolved in ammonia (7N in methanol, 3 mL) heated at 80° C. for 2 h The precipitated product was filtered washed through with methanol and diethyl ether followed by purification by preparative HPLC

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

Procedure: To the cold suspension of Pentyl-triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes. A solution of 5-Chloro-1H-indole-2-carbaldehyde in THF was added to the reaction mixture and stirred for 3 hours. The reaction mixture was treated with saturated ammonium chloride and ethyl acetate. The product was purified by column chromatography. stirred for 3 hours The product was purified by column chromatography

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

Procedure: 5-Chloroindole-2-carboxaldehyde was prepared starting from ethyl 5-chloroindole-2-carboxylate (7.4 g, 33 mmol) according to the procedure of Preparation 1, obtaining 2 g of a yellow solid, m.p.=208-209° C. The aldehyde (1.2 g, 6.7 mmol) was transformed in (E)-3-(5-chloro-2-indolyl)-2-propenaldehyde through the reaction with (formylmethylene)triphenylphosphorane (2 g, 6.7 mmol) following the procedure described in Preparation 2, obtaining 0.5 g of yellow powder, m.p.=207-209° C. (E)-3-(5-Chloro-2-indolyl)-2-propenaldehyde (0.5 g, 2.4 mmol) and DBU (0.75 ml, 5 mmol) were treated with methyl 2-methoxy-2-(triphenylphosphonium)acetate bromide (2.16 g, 5 mmol) according to the procedure of Example 1A to afford 250 mg (47%) of the title compound, m.p.=166-168° C. described in Preparation 2

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

Procedure: To the cold suspension of (4-methyl-pentyl)-triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes and then the solution of 5-chloro-1H-indole-2-carbaldehyde was added to the reaction mixture and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, 5-chloro-2-(5-methyl-hex-1-enyl)-1H-indole was purified by column chromatography. stirred for 3 hours The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The product, 5-chloro-2-(5-methyl-hex-1-enyl)-1H-indole was purified by column chromatography

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

Procedure: To the cold suspension of (4-methyl-pentyl)-triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes and then the solution of 5-chloro-1H-indole-2-carbaldehyde was added to the reaction mixture and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, 5-chloro-2-(5-methyl-hex-1-enyl)-1H-indole was purified by column chromatography. stirred for 3 hours The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The product, 5-chloro-2-(5-methyl-hex-1-enyl)-1H-indole was purified by column chromatography

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

Procedure: To the cold suspension of hexyl-triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes and then the solution of 5-chloro-1H-indole-2-carbaldehyde was added to the reaction mixture and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, 5-chloro-2-hept-1-enyl-1H-indole was purified by column chromatography. stirred for 3 hours The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The product, 5-chloro-2-hept-1-enyl-1H-indole was purified by column chromatography

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

Procedure: To the cold suspension of hexyl-triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes and then the solution of 5-chloro-1H-indole-2-carbaldehyde was added to the reaction mixture and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, 5-chloro-2-hept-1-enyl-1H-indole was purified by column chromatography. stirred for 3 hours The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The product, 5-chloro-2-hept-1-enyl-1H-indole was purified by column chromatography

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

Procedure: To the cold suspension of pentyl triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes and then the solution of 5-chloro-1H-indole-2-carbaldehyde was added to the reaction mixture and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, 5-chloro-2-hex-1-enyl-1H-indole was purified by column chromatography. stirred for 3 hours The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The product, 5-chloro-2-hex-1-enyl-1H-indole was purified by column chromatography

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

Procedure: To the cold suspension of pentyl triphenyl-phosphonium bromide in THF was added LiHMDS in THF and the mixture was stirred for 30 minutes and then the solution of 5-chloro-1H-indole-2-carbaldehyde was added to the reaction mixture and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The product, 5-chloro-2-hex-1-enyl-1H-indole was purified by column chromatography. stirred for 3 hours The reaction was quenched with saturated ammonium chloride solution extracted with ethyl acetate The product, 5-chloro-2-hex-1-enyl-1H-indole was purified by column chromatography

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

Procedure: 5-Chloro-1H-indole-2-carbaldehyde (0.15 g, 0.76 mmol), NaCNBH3 (0.040 g, 0.63 mmol) and Et3N (0.088 mL, 0.63 mmol) was added to a stirred solution of 3-amino-1H-pyrrole-2-carboxylic acid ethyl ester hydrochloride (0.12 g, 0.63 mmol) in methanol (3 mL). The resulting mixture was stirred at r.t. overnight. The reaction mixture was heated to 50° C. Additional NaCNBH3 (0.5 equiv.) was added and the mixture was stirred at 50° C. for 3 h. A few drops of HOAc was added, and after 1 h the reaction mixture was cooled to r.t. and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (2 mL) and methanol (2 mL). Benzoyl isothiocyanate (0.093 mL, 0.69 mmol) was added and after stirring at r.t. for 1 h the mixture was concentrated in vacuo. The residue was dissolved in ammonia (7N in methanol, 3 mL) and heated at 80° C. for 2 h. The precipitated product was filtered and washed through with methanol and diethyl ether, followed by purification by preparative HPLC, obtaining 0.063 g (30%) of the title compound as a solid. The reaction mixture was heated to 50° C the mixture was stirred at 50° C. for 3 h after 1 h the reaction mixture was cooled to r.t. was concentrated in vacuo The residue was dissolved in CH2Cl2 (2 mL) after stirring at r.t. for 1 h the mixture was concentrated in vacuo The residue was dissolved in ammonia (7N in methanol, 3 mL) heated at 80° C. for 2 h The precipitated product was filtered washed through with methanol and diethyl ether followed by purification by preparative HPLC

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

Procedure: 5-Chloro-1H-indole-2-carbaldehyde (0.15 g, 0.76 mmol), NaCNBH3 (0.040 g, 0.63 mmol) and Et3N (0.088 mL, 0.63 mmol) was added to a stirred solution of 3-amino-1H-pyrrole-2-carboxylic acid ethyl ester hydrochloride (0.12 g, 0.63 mmol) in methanol (3 mL). The resulting mixture was stirred at r.t. overnight. The reaction mixture was heated to 50° C. Additional NaCNBH3 (0.5 equiv.) was added and the mixture was stirred at 50° C. for 3 h. A few drops of HOAc was added, and after 1 h the reaction mixture was cooled to r.t. and was concentrated in vacuo. The residue was dissolved in CH2Cl2 (2 mL) and methanol (2 mL). Benzoyl isothiocyanate (0.093 mL, 0.69 mmol) was added and after stirring at r.t. for 1 h the mixture was concentrated in vacuo. The residue was dissolved in ammonia (7N in methanol, 3 mL) and heated at 80° C. for 2 h. The precipitated product was filtered and washed through with methanol and diethyl ether, followed by purification by preparative HPLC, obtaining 0.063 g (30%) of the title compound as a solid. The reaction mixture was heated to 50° C the mixture was stirred at 50° C. for 3 h after 1 h the reaction mixture was cooled to r.t. was concentrated in vacuo The residue was dissolved in CH2Cl2 (2 mL) after stirring at r.t. for 1 h the mixture was concentrated in vacuo The residue was dissolved in ammonia (7N in methanol, 3 mL) heated at 80° C. for 2 h The precipitated product was filtered washed through with methanol and diethyl ether followed by purification by preparative HPLC