4-amino-2-chloro-5-(2-trimethylsilylethynyl)benzonitrile

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

Procedure: To a solution of 238 (1.0 g, 4 mmol) in THF (100 mL) was added tetrabutylammonium fluoride (2.0 g, 7.6 mmol). The mixture was heated at 75° C. overnight then concentrated and the residue partitioned between EtOAc (500 mL) and H2O (50 mL). The organic layer was separated, washed with brine, concentrated to dryness in vacuo. The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc) to afford 700 mg (48%) 4-amino-2-chloro-5-ethynylbenzonitrile (240) as yellow solid: MS (ESI) m/z=177.0 [M+1]+. then concentrated the residue partitioned between EtOAc (500 mL) and H2O (50 mL) The organic layer was separated washed with brine concentrated to dryness in vacuo The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc)

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

Procedure: To a solution of 238 (1.0 g, 4 mmol) in THF (100 mL) was added tetrabutylammonium fluoride (2.0 g, 7.6 mmol). The mixture was heated at 75° C. overnight then concentrated and the residue partitioned between EtOAc (500 mL) and H2O (50 mL). The organic layer was separated, washed with brine, concentrated to dryness in vacuo. The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc) to afford 700 mg (48%) 4-amino-2-chloro-5-ethynylbenzonitrile (240) as yellow solid: MS (ESI) m/z=177.0 [M+1]+. then concentrated the residue partitioned between EtOAc (500 mL) and H2O (50 mL) The organic layer was separated washed with brine concentrated to dryness in vacuo The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom bottle was charged with 236 (2.78 g, 0.01 mol), CuI (95 mg, 0.5 mmol), Pd(PPh3)Cl2 (200 mg, 0.5 mmol), DIPEA (3.87 g, 0.03 mol) and ethynyltrimethylsilane (2.94 g, 0.03 mol). The mixture was heated under nitrogen atmosphere at 70° C. overnight then cooled and partitioned between EtOAc (500 mL) and H2O (100 mL). The organic layer was concentrated to dryness in vacuo. The crude was purified by SiO2 chromatography eluting with 10% EtOAc/petroleum ether to afford 1.2 g (48%) of 4-amino-2-chloro-5-((trimethylsilyl)ethynyl)benzonitrile (238) as brown solid: MS (ESI) m/z=249.1 [M+1]+ then cooled partitioned between EtOAc (500 mL) and H2O (100 mL) The organic layer was concentrated to dryness in vacuo The crude was purified by SiO2 chromatography eluting with 10% EtOAc/petroleum ether

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

Procedure: To a solution of 238 (1.0 g, 4 mmol) in THF (100 mL) was added tetrabutylammonium fluoride (2.0 g, 7.6 mmol). The mixture was heated at 75° C. overnight then concentrated and the residue partitioned between EtOAc (500 mL) and H2O (50 mL). The organic layer was separated, washed with brine, concentrated to dryness in vacuo. The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc) to afford 700 mg (48%) 4-amino-2-chloro-5-ethynylbenzonitrile (240) as yellow solid: MS (ESI) m/z=177.0 [M+1]+. then concentrated the residue partitioned between EtOAc (500 mL) and H2O (50 mL) The organic layer was separated washed with brine concentrated to dryness in vacuo The crude was purified by CombiFlash chromatography eluting with an EtOAc/petroleum ether gradient (10% to 45% EtOAc)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottom bottle was charged with 236 (2.78 g, 0.01 mol), CuI (95 mg, 0.5 mmol), Pd(PPh3)Cl2 (200 mg, 0.5 mmol), DIPEA (3.87 g, 0.03 mol) and ethynyltrimethylsilane (2.94 g, 0.03 mol). The mixture was heated under nitrogen atmosphere at 70° C. overnight then cooled and partitioned between EtOAc (500 mL) and H2O (100 mL). The organic layer was concentrated to dryness in vacuo. The crude was purified by SiO2 chromatography eluting with 10% EtOAc/petroleum ether to afford 1.2 g (48%) of 4-amino-2-chloro-5-((trimethylsilyl)ethynyl)benzonitrile (238) as brown solid: MS (ESI) m/z=249.1 [M+1]+ then cooled partitioned between EtOAc (500 mL) and H2O (100 mL) The organic layer was concentrated to dryness in vacuo The crude was purified by SiO2 chromatography eluting with 10% EtOAc/petroleum ether