3-amino-3-methylbutan-2-ol

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

Procedure: A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 3-amino-3-methylbutan-2-ol (0.05 g, 0.49 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), HOBT (0.041 g, 0.3 mmol) and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature overnight. The solvent was removed under reduced pressure at 70° C., the residue was triturated with water and then purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(3-hydroxy-2-methylbutan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 28%) as a yellow solid. MS: (M+H)+=413; 1H NMR (300 MHz, DMSO): δ 12.85 (s, 1H), 9.12 (s, 1H), 8.66 (d, 1H, J=8.7 Hz), 8.41 (s, 1H), 8.00-7.96 (m, 1H), 7.33 (dd, 1H, J=8.7, 1.5 Hz), 5.17 (d, 1H, J=5.7 Hz), 4.20 (s, 1H), 4.04-4.00 (m, 1H), 1.48 (s, 6H), 1.17 (d, 3H, J=6.6 Hz). The solvent was removed under reduced pressure at 70° C. the residue was triturated with water purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

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

Procedure: A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 3-amino-3-methylbutan-2-ol (0.05 g, 0.49 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), HOBT (0.041 g, 0.3 mmol) and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature overnight. The solvent was removed under reduced pressure at 70° C., the residue was triturated with water and then purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(3-hydroxy-2-methylbutan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 28%) as a yellow solid. MS: (M+H)+=413; 1H NMR (300 MHz, DMSO): δ 12.85 (s, 1H), 9.12 (s, 1H), 8.66 (d, 1H, J=8.7 Hz), 8.41 (s, 1H), 8.00-7.96 (m, 1H), 7.33 (dd, 1H, J=8.7, 1.5 Hz), 5.17 (d, 1H, J=5.7 Hz), 4.20 (s, 1H), 4.04-4.00 (m, 1H), 1.48 (s, 6H), 1.17 (d, 3H, J=6.6 Hz). The solvent was removed under reduced pressure at 70° C. the residue was triturated with water purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

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

Procedure: A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 3-amino-3-methylbutan-2-ol (0.05 g, 0.49 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), HOBT (0.041 g, 0.3 mmol) and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature overnight. The solvent was removed under reduced pressure at 70° C., the residue was triturated with water and then purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(3-hydroxy-2-methylbutan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 28%) as a yellow solid. MS: (M+H)+=413; 1H NMR (300 MHz, DMSO): δ 12.85 (s, 1H), 9.12 (s, 1H), 8.66 (d, 1H, J=8.7 Hz), 8.41 (s, 1H), 8.00-7.96 (m, 1H), 7.33 (dd, 1H, J=8.7, 1.5 Hz), 5.17 (d, 1H, J=5.7 Hz), 4.20 (s, 1H), 4.04-4.00 (m, 1H), 1.48 (s, 6H), 1.17 (d, 3H, J=6.6 Hz). The solvent was removed under reduced pressure at 70° C. the residue was triturated with water purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.

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

Procedure: A mixture of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.07 g, 0.3 mmol), 3-amino-3-methylbutan-2-ol (0.05 g, 0.49 mmol), EDCI (0.057 g, 0.3 mmol), DMAP (0.037 g, 0.3 mmol), HOBT (0.041 g, 0.3 mmol) and DIPEA (0.163 g, 1.26 mmol) in 10 mL of DMF was stirred at room temperature overnight. The solvent was removed under reduced pressure at 70° C., the residue was triturated with water and then purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions were: 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.) to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-N-(3-hydroxy-2-methylbutan-2-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.025 g, 28%) as a yellow solid. MS: (M+H)+=413; 1H NMR (300 MHz, DMSO): δ 12.85 (s, 1H), 9.12 (s, 1H), 8.66 (d, 1H, J=8.7 Hz), 8.41 (s, 1H), 8.00-7.96 (m, 1H), 7.33 (dd, 1H, J=8.7, 1.5 Hz), 5.17 (d, 1H, J=5.7 Hz), 4.20 (s, 1H), 4.04-4.00 (m, 1H), 1.48 (s, 6H), 1.17 (d, 3H, J=6.6 Hz). The solvent was removed under reduced pressure at 70° C. the residue was triturated with water purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm 15% acetonitrile/75% water (0.1% trifluoroacetic acid, v/v) initially, proceeding to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion over 9 min.