2-bromo-4,5-difluorobenzonitrile

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (100 mg, 0.458 mmol), ((R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-aminopropanamide (100 mg, 0.434 mmol) and DIEA (0.100 mL, 0.575 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. The mixture was purified by HPLC to give (R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-(5-bromo-4-cyano-2-fluorophenylamino)propanamide (59 mg). The mixture was purified by HPLC

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (85 mg, 0.390 mmol), (R)-tert-butyl 1-amino-1-oxo-3-(4-(pyridin-4-yl)phenyl)propan-2-ylcarbamate (72 mg, 0.299 mmol) and DIEA (0.200 mL, 1.15 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. HOAc (0.5 mL) was added. The mixture was purified by HPLC to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(4-(pyridin-4-yl)phenyl)propanamide (62 mg). The mixture was purified by HPLC

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (123 mg, 0.564 mmol), 2-amino-4,4,4-trifluorobutanamide (88 mg, 0.564 mmol) and DIEA (0.250 mL, 1.43 mmol) in DMSO (4 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column, which was eluted with 0-70% EtOAc in hexane to give 2-(5-bromo-4-cyano-2-fluorophenylamino)-4,4,4-trifluorobutanamide (90 mg). The organic phase was separated dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column, which was eluted with 0-70% EtOAc in hexane

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (150 mg, 0.688 mmol), (R)-2-amino-3-(pyridin-2-yl)propanamide hydrochloride (170 mg, 0.714 mmol) and DIEA (0.500 mL, 2.87 mmol) in DMSO (4 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(pyridin-2-yl)propanamide (274 mg) The organic phase was separated dried over Na2SO4 concentrated in vacuo

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (170 mg, 0.780 mmol), (R)-2-amino-2-cyclopropylacetamide hydrochloride (120 mg, 0.797 mmol) and DIEA (0.500 mL, 2.87 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-2-cyclopropylacetamide (197 mg) The organic phase was separated dried over Na2SO4 concentrated in vacuo

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (168 mg, 0.770 mmol), (R)-2-amino-3-methoxypropanamide hydrochloride (120 mg, 0.776 mmol) and DIEA (0.500 mL, 2.87 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column, which was eluted with 0-70% EtOAc in hexane to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-methoxypropanamide (52 mg). The organic phase was separated dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column, which was eluted with 0-70% EtOAc in hexane

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (218 mg, 1.00 mmol), (R)-2-amino-3-cyclopropylpropanamide (188 mg, 1.14 mmol) and DIEA (0.600 mL, 3.45 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2SO4, concentrated in vacuo to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-cyclopropylpropanamide (326 mg). The organic phase was separated washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (218 mg, 1.00 mmol), D-phenylalanine amide (185 mg, 1.12 mmol) and DIEA (0.600 mL, 3.45 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2SO4, concentrated in vacuo to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-phenylpropanamide (362 mg). The organic phase was separated washed with water dried over Na2SO4 concentrated in vacuo

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (218 mg, 1.00 mmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (214 mg, 1.00 mmol) and DIEA (0.300 mL, 1.72 mmol) in DMSO (2 mL) was stirred at 100 C for 18 h. Water was added to induce precipitation. The precipitate was collected and dried on vacuum to give tert-butyl (1S,2R)-2-(5-bromo-4-cyano-2-fluorophenylamino)cyclohexylcarbamate as a solid (385 mg). precipitation The precipitate was collected dried on vacuum

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (218 mg, 1.00 mmol), D-leucine amide hydrochloride (185 mg, 1.10 mmol) and DIEA (0.600 mL, 3.45 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. Water and EtOAc were added. The organic phase was separated, washed with water, dried over Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column, eluted with 0-50% EtOAc in hexane to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-4-methylpentanamide (175 mg). The organic phase was separated washed with water dried over Na2SO4 concentrated in vacuo The residue was purified by a silica gel column eluted with 0-50% EtOAc in hexane

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (100 mg, 0.458 mmol), ((R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-aminopropanamide (100 mg, 0.434 mmol) and DIEA (0.100 mL, 0.575 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. The mixture was purified by HPLC to give (R)-3-(4-(1H-imidazol-1-yl)phenyl)-2-(5-bromo-4-cyano-2-fluorophenylamino)propanamide (59 mg). The mixture was purified by HPLC

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

Procedure: A solution of 2-bromo-4,5-difluorobenzonitrile (85 mg, 0.390 mmol), (R)-tert-butyl 1-amino-1-oxo-3-(4-(pyridin-4-yl)phenyl)propan-2-ylcarbamate (72 mg, 0.299 mmol) and DIEA (0.200 mL, 1.15 mmol) in DMSO (3 mL) was stirred at 120 C for 18 h. HOAc (0.5 mL) was added. The mixture was purified by HPLC to give (R)-2-(5-bromo-4-cyano-2-fluorophenylamino)-3-(4-(pyridin-4-yl)phenyl)propanamide (62 mg). The mixture was purified by HPLC