2-fluoro-5-hydroxybenzonitrile

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

Procedure: The title compound was prepared by a procedure similar to that described for D4 starting from 3,4-difluorobenzaldehyde (188 mg, 1.32 mmol) and 2-fluoro-5-hydroxybenzonitrile.

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

Procedure: The title compound was prepared by a procedure similar to that described for D4 starting from 2-fluoro-5-formylbenzonitrile and 2-fluoro-5-hydroxybenzonitrile.

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

Procedure: When 2 mmol of 4,4-difluorocyclohexadienone and 4 mmol of potassium cyanide in 0.5 ml of dimethylformamide were mixed for 10 minutes at room temperature, 3-cyano-4-fluorophenol was formed in 90% yield. The spectral data of this new compound are as follows: Mass spectrum: m/e 137 (M+); 109 (M-CO, H); 82; 57.

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

Procedure: The compound of Preparation 200 was prepared according to the procedure of Preparation 199 substituting the corresponding ether for 2-Fluoro-5-methoxy-benzonitrile. The duration of reaction was between 1 and 24 hours. The compound of Preparation 200 was prepared The duration of reaction was between 1 and 24 hours

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

Procedure: The title compound was prepared according to the method described for Library Protocol 2 using 5-chloro-N-(2,4-dimethoxybenzyl)-2,4-difluoro-N-(pyrimidin-2-yl)benzenesulfonamide (WO2012004743) and 3-cyano-4-fluorophenol.

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

Procedure: To a solution of 2-fluoro-5-hydroxy-benzonitrile (Alfa Aesar, 137 mg, 1.0 mmol) was added 2-iodo-1,1,1,-trifluoroethane (117 L, 1.2 mmol) and potassium carbonate (165 mg, 1.2 mmol) in DMF (20 mL) and stirred at RT for 24 hours. The reaction was dissolved into EtOAc and washed with water three times and the combined organic layers were dried over anhydrous Na2SO4 and concentrated. The residue was purified by silica gel column chromatography using hexanes:ethyl acetate 5:1 to give the tile compound as white solid (105 mg, 48%). washed with water three times the combined organic layers were dried over anhydrous Na2SO4 concentrated The residue was purified by silica gel column chromatography

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

Procedure: The title compound was prepared by a procedure similar to that described for D4 starting from 3,4-difluorobenzaldehyde (188 mg, 1.32 mmol) and 2-fluoro-5-hydroxybenzonitrile.

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

Procedure: The title compound was prepared by a procedure similar to that described for D4 starting from 2-fluoro-5-formylbenzonitrile and 2-fluoro-5-hydroxybenzonitrile.

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

Procedure: When 2 mmol of 4,4-difluorocyclohexadienone and 4 mmol of potassium cyanide in 0.5 ml of dimethylformamide were mixed for 10 minutes at room temperature, 3-cyano-4-fluorophenol was formed in 90% yield. The spectral data of this new compound are as follows: Mass spectrum: m/e 137 (M+); 109 (M-CO, H); 82; 57.

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

Procedure: The compound of Preparation 200 was prepared according to the procedure of Preparation 199 substituting the corresponding ether for 2-Fluoro-5-methoxy-benzonitrile. The duration of reaction was between 1 and 24 hours. The compound of Preparation 200 was prepared The duration of reaction was between 1 and 24 hours