4-amino-2-fluoro-5-methoxybenzonitrile

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-amino-2-fluoro-5-methoxybenzonitrile (66 mg, 0.40 mmol) and 2-chloro-N-methyl-5-(trifluoromethyl)pyrimidin-4-amine (0.10 g, 0.47 mmol) in 1-butanol (2 mL) was added TFA (0.05 mL, 0.07 mmol). The reaction was stirred in a sealed tube at 75° C. for 2 h. The reaction was concentrated and the product was isolated by reverse-phase HPLC to give 2-fluoro-5-methoxy-4-(4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)benzonitrile. 1H NMR (400 MHz, DMSO) δ 8.57 (d, J=13.4, 2H), 8.34 (s, 1H), 8.29 (d, J=6.1, 1H), 7.56-7.42 (m, 3H), 3.93 (s, 3H), 2.95 (s, 3H); LRRK2 Ki=0.022. The reaction was concentrated the product was isolated by reverse-phase HPLC

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a pressure tube was added 4-bromo-5-fluoro-2-methoxyaniline (0.24 g, 1.1 mmol), zinc cyanide (0.10 g, 0.87 mmol), Pd2(dba)3 (100 mg, 0.11 mmol), DavePhos (86 mg, 0.22 mmol) and DMF (3 mL). The reaction was sealed and stirred at 100° C. for 6 hours. The reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography to give 4-amino-2-fluoro-5-methoxybenzonitrile (0.18 g, 77%). The reaction was sealed extracted with EtOAc The combined organic extracts were washed with brine dried over sodium sulfate filtered concentrated The crude product was purified by flash chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a pressure tube was added 4-bromo-5-fluoro-2-methoxyaniline (0.24 g, 1.1 mmol), zinc cyanide (0.10 g, 0.87 mmol), Pd2(dba)3 (100 mg, 0.11 mmol), DavePhos (86 mg, 0.22 mmol) and DMF (3 mL). The reaction was sealed and stirred at 100° C. for 6 hours. The reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography to give 4-amino-2-fluoro-5-methoxybenzonitrile (0.18 g, 77%). The reaction was sealed extracted with EtOAc The combined organic extracts were washed with brine dried over sodium sulfate filtered concentrated The crude product was purified by flash chromatography

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a pressure tube was added 4-bromo-5-fluoro-2-methoxyaniline (0.24 g, 1.1 mmol), zinc cyanide (0.10 g, 0.87 mmol), Pd2(dba)3 (100 mg, 0.11 mmol), DavePhos (86 mg, 0.22 mmol) and DMF (3 mL). The reaction was sealed and stirred at 100° C. for 6 hours. The reaction was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography to give 4-amino-2-fluoro-5-methoxybenzonitrile (0.18 g, 77%). The reaction was sealed extracted with EtOAc The combined organic extracts were washed with brine dried over sodium sulfate filtered concentrated The crude product was purified by flash chromatography