5-tert-butyl-1H-indol-6-amine

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

Procedure: Raney Ni (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (14.7 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine (B-24) as a gray solid (11 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylic acid (48 mg, 0.25 mmol), 5-tert-butyl-1H-indol-6-amine (48 mg, 0.25 mmol) in DMF (1 mL) was added HATU (106 mg, 0.28 mmol), followed by triethylamine (1064, 0.76 mmol) and the reaction mixture was heated at 80° C. for 16 h. The reaction mixture was then purified by reverse phase HPLC 10-99% ACN in water to give N-(5-tert-butyl-1H-indol-6-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxamide. MS m/z: 361.5 [M+H]+ The reaction mixture was then purified by reverse phase HPLC 10-99% ACN in water

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

Procedure: Raney Ni (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (14.7 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine as a gray solid (11 g). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether)

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

Procedure: Raney Ni (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (14.7 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine (B-24) as a gray solid (11 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether)

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

Procedure: Raney Nickel (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (15 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% ethyl acetate/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine as a gray solid (11 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% ethyl acetate/petroleum ether)

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

Procedure: Raney Nickel (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (15 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% ethyl acetate/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine as a gray solid (11 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% ethyl acetate/petroleum ether)

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

Procedure: A solution of (E)-2-(5-tert-butyl-2,4-dinitrophenyl)-N,N-dimethylethen-amine (5.3 g, 18 mmol) and tin (II) chloride dihydrate (37 g, 0.18 mol) in ethanol (200 mL) was heated at reflux overnight. The mixture was cooled to room temperature and the solvent was removed under vacuum. The residual slurry was diluted with water (500 mL) and was basifed with 10% aq. Na2CO3 to pH 8. The resulting suspension was extracted with ethyl acetate (3×100 mL). The ethyl acetate extract washed with water and brine, dried over Na2SO4, and concentrated. The residual solid washed with CH2Cl2 to afford a yellow powder, which was purified by column chromatography to give 5-tert-butyl-1H-indol-6-amine (0.40 g, 12%). 1H NMR (DMSO-d6) δ 10.34 (br s, 1H), 7.23 (s, 1H), 6.92 (s, 1H), 6.65 (s, 1H), 6.14 (s, 1H), 4.43 (br s, 2H), 2.48 (s, 9H); MS (ESI) m/e (M+H+) 189.1. at reflux overnight the solvent was removed under vacuum The residual slurry was diluted with water (500 mL) The resulting suspension was extracted with ethyl acetate (3×100 mL) The ethyl acetate extract washed with water and brine dried over Na2SO4 concentrated The residual solid washed with CH2Cl2 to afford a yellow powder, which was purified by column chromatography

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

Procedure: A solution of (E)-2-(5-tert-butyl-2,4-dinitrophenyl)-N,N-dimethylethen-amine (5.3 g, 18 mmol) and tin (II) chloride dihydrate (37 g, 0.18 mol) in ethanol (200 mL) was heated at reflux overnight. The mixture was cooled to room temperature and the solvent was removed under vacuum. The residual slurry was diluted with water (500 mL) and was basifed with 10% aq. Na2CO3 to pH 8. The resulting suspension was extracted with ethyl acetate (3×100 mL). The ethyl acetate extract washed with water and brine, dried over Na2SO4, and concentrated. The residual solid washed with CH2Cl2 to afford a yellow powder, which was purified by column chromatography to give 5-tert-butyl-1H-indol-6-amine (0.40 g, 12%). 1H NMR (DMSO-d6) δ 10.34 (br s, 1H), 7.23 (s, 1H), 6.92 (s, 1H), 6.65 (s, 1H), 6.14 (s, 1H), 4.43 (br s, 2H), 2.48 (s, 9H); MS (ESI) m/e (M+H+) 189.1. at reflux overnight the solvent was removed under vacuum The residual slurry was diluted with water (500 mL) The resulting suspension was extracted with ethyl acetate (3×100 mL) The ethyl acetate extract washed with water and brine dried over Na2SO4 concentrated The residual solid washed with CH2Cl2 to afford a yellow powder, which was purified by column chromatography

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

Procedure: Raney Ni (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (14.7 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine (B-24) as a gray solid (11 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether)

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

Procedure: Raney Nickel (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (15 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% ethyl acetate/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine as a gray solid (11 g, 87%). NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% ethyl acetate/petroleum ether)

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

Procedure: Raney Ni (3 g) was added to 5-tert-butyl-6-nitro-1H-indole (14.7 g, 67 mmol) in methanol (100 mL). The mixture was stirred under hydrogen (1 atm) at 30° C. for 3 h. The catalyst was filtered off. The filtrate was dried over Na2SO4 and concentrated. The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether) to give 5-tert-butyl-1H-indol-6-ylamine (B-24) as a gray solid (11 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 10.3 (br s, 1H), 7.2 (s, 1H), 6.9 (m, 1H), 6.6 (s, 1H), 6.1 (m, 1H), 4.4 (br s, 2H), 1.3 (s, 9H). The catalyst was filtered off The filtrate was dried over Na2SO4 concentrated The crude dark brown viscous oil was purified by column chromatography (10-20% EtOAc/petroleum ether)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxylic acid (48 mg, 0.25 mmol), 5-tert-butyl-1H-indol-6-amine (48 mg, 0.25 mmol) in DMF (1 mL) was added HATU (106 mg, 0.28 mmol), followed by triethylamine (1064, 0.76 mmol) and the reaction mixture was heated at 80° C. for 16 h. The reaction mixture was then purified by reverse phase HPLC 10-99% ACN in water to give N-(5-tert-butyl-1H-indol-6-yl)-4-oxo-1,4-dihydro-1,7-naphthyridine-3-carboxamide. MS m/z: 361.5 [M+H]+ The reaction mixture was then purified by reverse phase HPLC 10-99% ACN in water