4-BROMO-7-FLUOROINDOLE

At -40°C, vinylmagnesium bromide (300mL of 1.0M solution in THF, 300mmol) was added dropwise to a solution of 3-nitro-4-fluoro-bromobenzene (22 g, 100mmol) in THF (700ml_). After 1 h at -40°C, the mixture was quenched by aqueous NHAt -40° C., vinylmagnesium bromide (300 mL of 1.0M solution in THF, 300 mmol) was added dropwise to a solution of 3-nitro-4-fluoro-bromobenzene (22 g, 100 mmol) in THF (700 mL). After 1 h at -40° C., the mixture was quenched by aqueous NHAt -40 °C, vinylmagnesium bromide (75 mmol) in tetrahydrofuran (75 mL) was added dropwise, in the course of 30 min, to a solution of 4-bromo-1-fluoro-2-nitrobenzene (5.5 g, 25 mmol) in tetrahydrofuran (100 mL). After 1 h at -40 °C, the mixture was poured into a saturated aqueous solution (50 mL) of ammonium chloride. The organic layer was evaporated. The crude was submitted to flash chromatography through silica gel to obtain 1.2 g (22percent yield) of 4-bromo-7-fluoro-1H-indole.a) 2-(Bromomethyl)-4-chloro-1 -(4-chloro-2-fluorophenethyl)benzeneAt -40 °C, vinylmagnesium bromide (75 mmol) in tetrahydrofuran (75 ml_) was added dropwise. in the course of 30 min, to a solution of 4-bromo-1 -fluoro-2- nitrobenzene (5.5 g, 25 mmol) in tetrahydrofuran (100 ml_). After 1 h at -40 °C, the mixture was poured into a saturated aqueous solution (50 ml_) of ammonium chloride. The organic layer was evaporated. The crude was submitted to flash chromatography through silica gel to obtain 1 .2 g (22percent yield) of 4-bromo-7-fluoro- 1 H-indole.N4 -(5-cyclopropyl-lH-pyrazol-3-yl)- N2 -((7-fluoro-lH-indol-4-yl)methyl)pyrimidine-2, 4-diamine (1-47) step 1 : To a solution of 4-bromo-l -fluoro-2-nitrobenzene (1.1 g, 5.0 mmol) in THF (20 mL) at -40 °C under nitrogen atmosphere was added slowly vinylmagnesium bromide (1 M in THF, 15.5 mL, 15.5 mmol). The reaction mixture was stirred for 1.5 h then quenched with saturated NH4C1 aqueous solution (10 mL). The mixture was partitioned between EtO Ac (300 mL) and water (50 mL). The organic layer was separated, washed with brine, dried (MgS04), filtered and evaporated in vacuo. The residue was purified by S1O2 chromatography eluting with 2.5percent EtO Ac/petroleum ether to afford 0.125 g (12percent) of 4- bromo-7-fluoro-lH-indole (110) as brown oil: MS (ESI) m/z = 214 [M-l] +.To 2.42 g of 3-bromo-6-fluoronitrobenzene (B9.1) in -30 mL THF at -78°C was added 37 mL 1.0 M vinylmagnesium bromide (in THF). The reaction was stirred at -78°C for 10 minutes and then at -40°C for 1.5 hours. The reaction mixture was quenched with saturated NHAt -40°C, vinylmagnesium bromide (300mL of 1.0M solution in THF, 300mmol) was added dropwise to a solution of 3-nitro-4-fluoro-bromobenzene (22 g, 100mmol) in THF (700ml_). After 1 h at -40°C, the mixture was quenched by aqueous NHAt -40° C., vinylmagnesium bromide (300 mL of 1.0M solution in THF, 300 mmol) was added dropwise to a solution of 3-nitro-4-fluoro-bromobenzene (22 g, 100 mmol) in THF (700 mL). After 1 h at -40° C., the mixture was quenched by aqueous NHAt -40 °C, vinylmagnesium bromide (75 mmol) in tetrahydrofuran (75 mL) was added dropwise, in the course of 30 min, to a solution of 4-bromo-1-fluoro-2-nitrobenzene (5.5 g, 25 mmol) in tetrahydrofuran (100 mL). After 1 h at -40 °C, the mixture was poured into a saturated aqueous solution (50 mL) of ammonium chloride. The organic layer was evaporated. The crude was submitted to flash chromatography through silica gel to obtain 1.2 g (22percent yield) of 4-bromo-7-fluoro-1H-indole.a) 2-(Bromomethyl)-4-chloro-1 -(4-chloro-2-fluorophenethyl)benzeneAt -40 °C, vinylmagnesium bromide (75 mmol) in tetrahydrofuran (75 ml_) was added dropwise. in the course of 30 min, to a solution of 4-bromo-1 -fluoro-2- nitrobenzene (5.5 g, 25 mmol) in tetrahydrofuran (100 ml_). After 1 h at -40 °C, the mixture was poured into a saturated aqueous solution (50 ml_) of ammonium chloride. The organic layer was evaporated. The crude was submitted to flash chromatography through silica gel to obtain 1 .2 g (22percent yield) of 4-bromo-7-fluoro- 1 H-indole.N4 -(5-cyclopropyl-lH-pyrazol-3-yl)- N2 -((7-fluoro-lH-indol-4-yl)methyl)pyrimidine-2, 4-diamine (1-47) step 1 : To a solution of 4-bromo-l -fluoro-2-nitrobenzene (1.1 g, 5.0 mmol) in THF (20 mL) at -40 °C under nitrogen atmosphere was added slowly vinylmagnesium bromide (1 M in THF, 15.5 mL, 15.5 mmol). The reaction mixture was stirred for 1.5 h then quenched with saturated NH4C1 aqueous solution (10 mL). The mixture was partitioned between EtO Ac (300 mL) and water (50 mL). The organic layer was separated, washed with brine, dried (MgS04), filtered and evaporated in vacuo. The residue was purified by S1O2 chromatography eluting with 2.5percent EtO Ac/petroleum ether to afford 0.125 g (12percent) of 4- bromo-7-fluoro-lH-indole (110) as brown oil: MS (ESI) m/z = 214 [M-l] +.To 2.42 g of 3-bromo-6-fluoronitrobenzene (B9.1) in -30 mL THF at -78°C was added 37 mL 1.0 M vinylmagnesium bromide (in THF). The reaction was stirred at -78°C for 10 minutes and then at -40°C for 1.5 hours. The reaction mixture was quenched with saturated NH

Molecular Weight:214.03
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:212.95894
Monoisotopic Mass:212.95894
Topological Polar Surface Area:15.8
Heavy Atom Count:11
Complexity:153
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes