5-fluoro-1H-indole-2-carbaldehyde

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

Procedure: To a 100 mL round-bottom flask was added 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 3.84 mmol), methanol (40 mL), p-toluene sulfonylmethyl isocyanide (0.826 g, 4.23 mmol), followed by potassium carbonate (0.68 g, 4.92 mmol). The reaction mixture was stirred at reflux for about 1.5 hour and followed by TLC. The solvent was then evaporated and saturated aq. NaHCO3 was added. The resultant suspension was extracted with CH2Cl2 (2×20 mL). Combined organic layers were washed with brine, dried (anhydrous Na2SO4), and concentrated to leave a yellow solid. Crude product was further purified by silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-(5-fluoro-1H-indol-2-yl)oxazole 48 (0.202 g, 72% yield). MS (ES) m/z 203 (M+H+). at reflux for about 1.5 hour The solvent was then evaporated saturated aq. NaHCO3 was added The resultant suspension was extracted with CH2Cl2 (2×20 mL) Combined organic layers were washed with brine dried (anhydrous Na2SO4) concentrated to leave a yellow solid Crude product was further purified by silica-column chromatographed (Biotage)

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

Procedure: To a stirred solution of crude (5-fluoro-1H-indol-2-yl)methanol 46 (1.55 g, 9.39 mmol) in anhydrous CH2Cl2 (50 mL) at cold-bath temperature (0° C.) was added portionwise pyridinium chlorochromate (PCC) (2.22 g, 10.29 mmol). Reaction was stirred at ambient temperature for 4 hours. Reaction was diluted with CH2Cl2 and filtered through a pad of celite and washed with CH2Cl2. After evaporation of solvent, crude product was silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 41% yield). Reaction Reaction filtered through a pad of celite washed with CH2Cl2 After evaporation of solvent, crude product chromatographed (Biotage)

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

Procedure: To a stirred solution of crude (5-fluoro-1H-indol-2-yl)methanol 46 (1.55 g, 9.39 mmol) in anhydrous CH2Cl2 (50 mL) at cold-bath temperature (0° C.) was added portionwise pyridinium chlorochromate (PCC) (2.22 g, 10.29 mmol). Reaction was stirred at ambient temperature for 4 hours. Reaction was diluted with CH2Cl2 and filtered through a pad of celite and washed with CH2Cl2. After evaporation of solvent, crude product was silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 41% yield). Reaction Reaction filtered through a pad of celite washed with CH2Cl2 After evaporation of solvent, crude product chromatographed (Biotage)

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

Procedure: To a 100 mL round-bottom flask was added 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 3.84 mmol), methanol (40 mL), p-toluene sulfonylmethyl isocyanide (0.826 g, 4.23 mmol), followed by potassium carbonate (0.68 g, 4.92 mmol). The reaction mixture was stirred at reflux for about 1.5 hour and followed by TLC. The solvent was then evaporated and saturated aq. NaHCO3 was added. The resultant suspension was extracted with CH2Cl2 (2×20 mL). Combined organic layers were washed with brine, dried (anhydrous Na2SO4), and concentrated to leave a yellow solid. Crude product was further purified by silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-(5-fluoro-1H-indol-2-yl)oxazole 48 (0.202 g, 72% yield). MS (ES) m/z 203 (M+H+). at reflux for about 1.5 hour The solvent was then evaporated saturated aq. NaHCO3 was added The resultant suspension was extracted with CH2Cl2 (2×20 mL) Combined organic layers were washed with brine dried (anhydrous Na2SO4) concentrated to leave a yellow solid Crude product was further purified by silica-column chromatographed (Biotage)

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

Procedure: To a stirred solution of crude (5-fluoro-1H-indol-2-yl)methanol 46 (1.55 g, 9.39 mmol) in anhydrous CH2Cl2 (50 mL) at cold-bath temperature (0° C.) was added portionwise pyridinium chlorochromate (PCC) (2.22 g, 10.29 mmol). Reaction was stirred at ambient temperature for 4 hours. Reaction was diluted with CH2Cl2 and filtered through a pad of celite and washed with CH2Cl2. After evaporation of solvent, crude product was silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 41% yield). Reaction Reaction filtered through a pad of celite washed with CH2Cl2 After evaporation of solvent, crude product chromatographed (Biotage)

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

Procedure: A reaction mixture of 4-amino-5-imidazolecarboxamide hydrochloride (0.48 g, 2.94 mmol), 5-fluoro-1H-indole-2-carbaldehyde (0.40 g, 2.45 mmol), and NaCNBH3 (0.15 g, 2.45 mmol) in methanol (3 mL) was stirred at r.t. for 1 h. Additional 5-fluoro-1H-indole-2-carbaldehyde (0.42 equiv.) was added and after stirring at r.t. for 1 h the mixture was concentrated in vacuo. The residue was dissolved in ethyl acetate and washed with water. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were dried (MgSO4) and concentrated. The crude product was purified by flash column chromatography (CH2Cl2/methanol gradient; 0 to 20% methanol), obtaining 0.75 g (70%) of the title compound. MS (ESI) m/z 272 (M−1). after stirring at r.t. for 1 h the mixture was concentrated in vacuo The residue was dissolved in ethyl acetate washed with water The aqueous phase was extracted twice with ethyl acetate The combined organic layers were dried (MgSO4) concentrated The crude product was purified by flash column chromatography (CH2Cl2/methanol gradient; 0 to 20% methanol)

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

Procedure: To a 100 mL round-bottom flask was added 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 3.84 mmol), methanol (40 mL), p-toluene sulfonylmethyl isocyanide (0.826 g, 4.23 mmol), followed by potassium carbonate (0.68 g, 4.92 mmol). The reaction mixture was stirred at reflux for about 1.5 hour and followed by TLC. The solvent was then evaporated and saturated aq. NaHCO3 was added. The resultant suspension was extracted with CH2Cl2 (2×20 mL). Combined organic layers were washed with brine, dried (anhydrous Na2SO4), and concentrated to leave a yellow solid. Crude product was further purified by silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-(5-fluoro-1H-indol-2-yl)oxazole 48 (0.202 g, 72% yield). MS (ES) m/z 203 (M+H+). at reflux for about 1.5 hour The solvent was then evaporated saturated aq. NaHCO3 was added The resultant suspension was extracted with CH2Cl2 (2×20 mL) Combined organic layers were washed with brine dried (anhydrous Na2SO4) concentrated to leave a yellow solid Crude product was further purified by silica-column chromatographed (Biotage)

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

Procedure: To a 100 mL round-bottom flask was added 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 3.84 mmol), methanol (40 mL), p-toluene sulfonylmethyl isocyanide (0.826 g, 4.23 mmol), followed by potassium carbonate (0.68 g, 4.92 mmol). The reaction mixture was stirred at reflux for about 1.5 hour and followed by TLC. The solvent was then evaporated and saturated aq. NaHCO3 was added. The resultant suspension was extracted with CH2Cl2 (2×20 mL). Combined organic layers were washed with brine, dried (anhydrous Na2SO4), and concentrated to leave a yellow solid. Crude product was further purified by silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-(5-fluoro-1H-indol-2-yl)oxazole 48 (0.202 g, 72% yield). MS (ES) m/z 203 (M+H+). at reflux for about 1.5 hour The solvent was then evaporated saturated aq. NaHCO3 was added The resultant suspension was extracted with CH2Cl2 (2×20 mL) Combined organic layers were washed with brine dried (anhydrous Na2SO4) concentrated to leave a yellow solid Crude product was further purified by silica-column chromatographed (Biotage)

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

Procedure: To a stirred solution of crude (5-fluoro-1H-indol-2-yl)methanol 46 (1.55 g, 9.39 mmol) in anhydrous CH2Cl2 (50 mL) at cold-bath temperature (0° C.) was added portionwise pyridinium chlorochromate (PCC) (2.22 g, 10.29 mmol). Reaction was stirred at ambient temperature for 4 hours. Reaction was diluted with CH2Cl2 and filtered through a pad of celite and washed with CH2Cl2. After evaporation of solvent, crude product was silica-column chromatographed (Biotage) using Acetone:Hexane as an eluent to yield 5-fluoro-1H-indole-2-carbaldehyde 47 (0.627 g, 41% yield). Reaction Reaction filtered through a pad of celite washed with CH2Cl2 After evaporation of solvent, crude product chromatographed (Biotage)

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

Procedure: p-Toluenesulfonyl chloride (2.445 g, 12.82 mmol), N,N-dimethyl-4-aminopyridine (0.196 g, 1.603 mmol) and triethylamine (2.253 ml, 16.03 mmol) were added to a solution of 5-fluoro-1H-indole-2-carbaldehyde (0.523 g, 3.21 mmol) in dichloromethane (10 ml) and stirred at room temperature for 20 hours. After reaction, the mixture was poured into saturated sodium bicarbonate aqueous solution, and the aqueous phase was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (10:1) to give 823 mg (81% yield) of the title compound as a white crystal: After reaction the aqueous phase was extracted with ethyl acetate The organic layer was dried over magnesium sulfate concentrated in vacuo The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (10:1)

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

Procedure: Lithium aluminium hydride (0.094 g, 2.488 mmol) was added to a solution of 5-fluoro-N-methoxy-N-methyl-1H-indole-2-carboxamide (0.691 g, 3.11 mmol) in tetrahydrofuran (10 ml) at 0° C. and stirred for 1 hour. The reaction mixture was cooled to 0° C. and 25% ammonia solution was added dropwise to the reaction mixture until lithium aluminium hydride color turn gray to white. Then dichloromethane and cerite was added to the reaction mixture and stirred for 30 min. The mixture was filtered through a pad of Celite and concentrated in vacuo to give 523 mg of the crude title compound. This was used for the next step without further purification: stirred for 30 min The mixture was filtered through a pad of Celite concentrated in vacuo

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

Procedure: Lithium aluminium hydride (0.094 g, 2.488 mmol) was added to a solution of 5-fluoro-N-methoxy-N-methyl-1H-indole-2-carboxamide (0.691 g, 3.11 mmol) in tetrahydrofuran (10 ml) at 0° C. and stirred for 1 hour. The reaction mixture was cooled to 0° C. and 25% ammonia solution was added dropwise to the reaction mixture until lithium aluminium hydride color turn gray to white. Then dichloromethane and cerite was added to the reaction mixture and stirred for 30 min. The mixture was filtered through a pad of Celite and concentrated in vacuo to give 523 mg of the crude title compound. This was used for the next step without further purification: stirred for 30 min The mixture was filtered through a pad of Celite concentrated in vacuo