tert-butyl N-[(1-aminocyclopropyl)methyl]carbamate

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

Procedure: To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.10 g, 0.32 mmol), EDCI (0.123 g, 0.64 mmol), DMAP (0.122 g, 1 mmol) and DIPEA (0.11 g, 0.90 mmol) in 6 mL of DMF was added tert-butyl (1-aminocyclopropyl)methylcarbamate (0.20 g, 1.07 mmol) in one portion at room temperature and stirred for 16 hours. The mixture was poured into 50 mL of water, and filtered. The filter cake was washed with water, dried and used in the next step without further purification. MS: (M+H)+=480.2. filtered The filter cake was washed with water dried used in the next step without further purification

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

Procedure: To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.10 g, 0.32 mmol), EDCI (0.123 g, 0.64 mmol), DMAP (0.122 g, 1 mmol) and DIPEA (0.11 g, 0.90 mmol) in 6 mL of DMF was added tert-butyl (1-aminocyclopropyl)methylcarbamate (0.20 g, 1.07 mmol) in one portion at room temperature and stirred for 16 hours. The mixture was poured into 50 mL of water, and filtered. The filter cake was washed with water, dried and used in the next step without further purification. MS: (M+H)+=480.2. filtered The filter cake was washed with water dried used in the next step without further purification

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

Procedure: To a stirred solution of [1-(tert-butoxycarbonylamino-methyl)-cyclopropyl]-carbamic acid benzyl ester (0.912 g, 2.85 mmol) in 120 mL of methanol was added 10% Pd on carbon (200 mg) in one portion at room temperature. Then the mixture was degassed by bubbling hydrogen for 5 minutes then stirred under a hydrogen atmosphere at room temperature for 16 hours. The mixture was filtered to remove the catalyst and the filtrate was evaporated at 40° C. under reduced pressure to give tert-butyl (1-aminocyclopropyl)methylcarbamate (0.4 g, 75.4%) as a colorless oil which was used into next step without further purification. MS: (M+H)+=187.2. Then the mixture was degassed by bubbling hydrogen for 5 minutes The mixture was filtered to remove the catalyst the filtrate was evaporated at 40° C. under reduced pressure

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

Procedure: To a stirred solution of [1-(tert-butoxycarbonylamino-methyl)-cyclopropyl]-carbamic acid benzyl ester (0.912 g, 2.85 mmol) in 120 mL of methanol was added 10% Pd on carbon (200 mg) in one portion at room temperature. Then the mixture was degassed by bubbling hydrogen for 5 minutes then stirred under a hydrogen atmosphere at room temperature for 16 hours. The mixture was filtered to remove the catalyst and the filtrate was evaporated at 40° C. under reduced pressure to give tert-butyl (1-aminocyclopropyl)methylcarbamate (0.4 g, 75.4%) as a colorless oil which was used into next step without further purification. MS: (M+H)+=187.2. Then the mixture was degassed by bubbling hydrogen for 5 minutes The mixture was filtered to remove the catalyst the filtrate was evaporated at 40° C. under reduced pressure

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

Procedure: To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.10 g, 0.32 mmol), EDCI (0.123 g, 0.64 mmol), DMAP (0.122 g, 1 mmol) and DIPEA (0.11 g, 0.90 mmol) in 6 mL of DMF was added tert-butyl (1-aminocyclopropyl)methylcarbamate (0.20 g, 1.07 mmol) in one portion at room temperature and stirred for 16 hours. The mixture was poured into 50 mL of water, and filtered. The filter cake was washed with water, dried and used in the next step without further purification. MS: (M+H)+=480.2. filtered The filter cake was washed with water dried used in the next step without further purification

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

Procedure: To a stirred solution of [1-(tert-butoxycarbonylamino-methyl)-cyclopropyl]-carbamic acid benzyl ester (0.912 g, 2.85 mmol) in 120 mL of methanol was added 10% Pd on carbon (200 mg) in one portion at room temperature. Then the mixture was degassed by bubbling hydrogen for 5 minutes then stirred under a hydrogen atmosphere at room temperature for 16 hours. The mixture was filtered to remove the catalyst and the filtrate was evaporated at 40° C. under reduced pressure to give tert-butyl (1-aminocyclopropyl)methylcarbamate (0.4 g, 75.4%) as a colorless oil which was used into next step without further purification. MS: (M+H)+=187.2. Then the mixture was degassed by bubbling hydrogen for 5 minutes The mixture was filtered to remove the catalyst the filtrate was evaporated at 40° C. under reduced pressure

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

Procedure: To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (0.10 g, 0.32 mmol), EDCI (0.123 g, 0.64 mmol), DMAP (0.122 g, 1 mmol) and DIPEA (0.11 g, 0.90 mmol) in 6 mL of DMF was added tert-butyl (1-aminocyclopropyl)methylcarbamate (0.20 g, 1.07 mmol) in one portion at room temperature and stirred for 16 hours. The mixture was poured into 50 mL of water, and filtered. The filter cake was washed with water, dried and used in the next step without further purification. MS: (M+H)+=480.2. filtered The filter cake was washed with water dried used in the next step without further purification

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

Procedure: To a stirred solution of [1-(tert-butoxycarbonylamino-methyl)-cyclopropyl]-carbamic acid benzyl ester (0.912 g, 2.85 mmol) in 120 mL of methanol was added 10% Pd on carbon (200 mg) in one portion at room temperature. Then the mixture was degassed by bubbling hydrogen for 5 minutes then stirred under a hydrogen atmosphere at room temperature for 16 hours. The mixture was filtered to remove the catalyst and the filtrate was evaporated at 40° C. under reduced pressure to give tert-butyl (1-aminocyclopropyl)methylcarbamate (0.4 g, 75.4%) as a colorless oil which was used into next step without further purification. MS: (M+H)+=187.2. Then the mixture was degassed by bubbling hydrogen for 5 minutes The mixture was filtered to remove the catalyst the filtrate was evaporated at 40° C. under reduced pressure