5-fluoro-1H-indole-6-carbonitrile

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of oxalyl chloride (0.68 mL) in DCM (10 mL) at 0° C. was dropwise added a solution of DMF (0.60 mL) in DCM (2 mL). The mixture was stirred for 0.5 h at 0° C. and then 5-fluoro-1H-indole-6-carbonitrile (D151) (250 mg) in DCM (3 mL) was added in one portion. The reaction mixture was allowed to warm to rt and stirred overnight. Afterwards, the reaction mixture was added with 2 M aqueous NaOH (30 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with water, dried over anhydrous sodium sulfate, and then concentrated under vacuo to give the designed product 5-fluoro-3-formyl-1H-indole-6-carbonitrile (D152) (280 mg), which was used without purification. MS (ES): C10H5FN2O requires 188.0; found 189.1 (M+H+). to warm to rt stirred overnight extracted with EtOAc (3×50 mL) The combined organic layers were washed with water dried over anhydrous sodium sulfate concentrated under vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a microwave reaction vessel was added 5-fluoro-6-iodo-1H-indole (1 g), potassium ferrocyanide (1.41 g), Na2CO3 (0.80 g), PdCl2(dppf)-CH2Cl2 adduct (0.31 g) and N,N-dimethylacetamide (DMA). The reaction vessel was then sealed and heated in Biotage Initiator using initial high to 140° C. for 2 hours. After cooling the reaction, the solvent was evaporated and the residue was partitioned between water (50 mL) and ethyl acetate (50 mL). The insolubles were filtered, the organics were evaporated and the residue was chromatographed on silica gel to give the designed product 5-fluoro-1H-indole-6-carbonitrile (D151) (0.25 g). MS (ES): C9H5FN2 requires 160.0; found 161.1 (M+H+). To a microwave reaction vessel The reaction vessel was then sealed heated in Biotage Initiator high to 140° C. for 2 hours After cooling the reaction the solvent was evaporated the residue was partitioned between water (50 mL) and ethyl acetate (50 mL) The insolubles were filtered the organics were evaporated the residue was chromatographed on silica gel