2-fluoro-6-(methylamino)benzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 2,6-Difluorobenzonitrile, 2.78 g (20 mmol) and 5 ml (60 mmol) of 40% aqueous methylamine in 50 ml DMF is stirred at room temperature for 1 hr., poured into water and the product is collected, 2.4 g m.p. 130°-132° C. the product is collected

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

Procedure: To a stirred solution of 2-fluoro-6-methylamino-benzonitrile (1.5 g, 10 mmol) in THF (50 mL) at −78° C. was added LiHMDS (1M in THF, 16 mL, 16 mmol) dropwise over 5 min. The resulting pale yellow solution was stirred for an additional 30 min, then methanesulfonyl chloride (1.16 mL, 15 mmol) was added. After 30 min, the reaction mixture was quenched with saturated NH4Cl (1 mL), diluted with ethyl acetate (100 mL), dried (MgSO4), filtered and concentrated to give viscous yellow oil. The crude product was purified on silica gel column (2:3 EtOAc/hexanes) to give the title compound as a white solid (1.5936 g, 70% yield). 1HNMR (500 MHz, CDCl3) δ: 7.65–7.61 (1H, m), 7.86 (1H, d, J=8.24 Hz), 7.22 (1H, t, J=8.24 Hz), 3.38 (3H, s), 3.13 (3H, s). HRMS (ESI) calcd for C17H22FN2O7S (M+H): 417.1132; found: 417.1116. After 30 min the reaction mixture was quenched with saturated NH4Cl (1 mL) diluted with ethyl acetate (100 mL) dried (MgSO4) filtered concentrated to give viscous yellow oil The crude product was purified on silica gel column (2:3 EtOAc/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 2,6-difluorobenzonitrile (3.5 g, 25.2 mmol) in ethanol (40 mL) was added 2 mL of methylamine (40 wt %, in H2O) and heated at 80° C. for 2 h. The mixture was then diluted with water and the resulting slurry extracted with dichloromethane (3×50 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated to give the title product as a white solid (3.77 g, 99.6% yield). 1HNMR (500 MHz, CDCl3) δ: 7.35–7.31 (1H, m), 6.41–6.38 (2H, m), 4.74 (1H, br s), 2.93 (3H, d, J=5.19 Hz). LCMS calcd for C8H8FN2 (M+H): 151.07. the resulting slurry extracted with dichloromethane (3×50 mL) The combined organic extracts were dried (Na2SO4) filtered concentrated