1-苄基氮杂-4-甲腈

反应条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Polyphosphoric acid (PPA) (10 g) was heated to 160° C. Intermediate (1) (0.0467 mol) and 2,3-diaminopyridine (0.0513 mol) were added. The mixture was stirred at 180° C. for 1 hour, poured out on K2CO3 solid and ice, washed with K2CO3 10% and extracted with DCM. The aqueous layer was washed with DCM. The organic layer was dried, filtered and the solvent was evaporated.This fraction was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5). The pure fractions were collected and the solvent was evaporated. Part of this fraction (6 g) was crystallized from DIPE and 2-propanone. The precipitate was filtered off and dried, yielding 3.16 g of (±)-2-[hexahydro-1-(phenylmethyl)-1H-azepin-4-yl]-1H-imidazo[4,5-b]pyridine (compound 69). poured out on K2CO3 solid and ice washed with K2CO3 10% extracted with DCM The aqueous layer was washed with DCM The organic layer was dried filtered was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5) The pure fractions were collected the solvent was evaporated Part of this fraction (6 g) was crystallized from DIPE and 2-propanone The precipitate was filtered off dried

反应条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Polyphosphoric acid (PPA) (10 g) was heated to 160° C. Intermediate (1) (0.0467 mol) and 2,3-diaminopyridine (0.0513 mol) were added. The mixture was stirred at 180° C. for 1 hour, poured out on K2CO3 solid and ice, washed with K2CO3 10% and extracted with DCM. The aqueous layer was washed with DCM. The organic layer was dried, filtered and the solvent was evaporated.This fraction was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5). The pure fractions were collected and the solvent was evaporated. Part of this fraction (6 g) was crystallized from DIPE and 2-propanone. The precipitate was filtered off and dried, yielding 3.16 g of (±)-2-[hexahydro-1-(phenylmethyl)-1H-azepin-4-yl]-1H-imidazo[4,5-b]pyridine (compound 69). poured out on K2CO3 solid and ice washed with K2CO3 10% extracted with DCM The aqueous layer was washed with DCM The organic layer was dried filtered was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5) The pure fractions were collected the solvent was evaporated Part of this fraction (6 g) was crystallized from DIPE and 2-propanone The precipitate was filtered off dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.2 mol) and 4-toluene-sulfonylmethyl isocyanide (0.25 mol) in DMF (200 ml) was stirred at 0° C. A solution of potassium tert-butoxide (0.4 mol) in a mixture of 2-methyl-2-propanol (200 ml) and 1,2-dimethoxyethane (200 ml) was added dropwise at 0° C. The mixture was allowed to reach room temperature and stirring was continued for 1 hour. The mixture was stirred in water and this mixture was extracted with DCM. The separated organic layer was dried, filtered and the solvent was evaporated, yielding 48 g of (±)-hexahydro-1-(phenylmethyl)-1H-azepine-4-carbonitrile (intermediate 1). was added dropwise at 0° C to reach room temperature stirring this mixture was extracted with DCM The separated organic layer was dried filtered the solvent was evaporated

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.2 mol) and 4-toluene-sulfonylmethyl isocyanide (0.25 mol) in DMF (200 ml) was stirred at 0° C. A solution of potassium tert-butoxide (0.4 mol) in a mixture of 2-methyl-2-propanol (200 ml) and 1,2-dimethoxyethane (200 ml) was added dropwise at 0° C. The mixture was allowed to reach room temperature and stirring was continued for 1 hour. The mixture was stirred in water and this mixture was extracted with DCM. The separated organic layer was dried, filtered and the solvent was evaporated, yielding 48 g of (±)-hexahydro-1-(phenylmethyl)-1H-azepine-4-carbonitrile (intermediate 1). was added dropwise at 0° C to reach room temperature stirring this mixture was extracted with DCM The separated organic layer was dried filtered the solvent was evaporated

反应条件: temp:180.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Polyphosphoric acid (PPA) (10 g) was heated to 160° C. Intermediate (1) (0.0467 mol) and 2,3-diaminopyridine (0.0513 mol) were added. The mixture was stirred at 180° C. for 1 hour, poured out on K2CO3 solid and ice, washed with K2CO3 10% and extracted with DCM. The aqueous layer was washed with DCM. The organic layer was dried, filtered and the solvent was evaporated.This fraction was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5). The pure fractions were collected and the solvent was evaporated. Part of this fraction (6 g) was crystallized from DIPE and 2-propanone. The precipitate was filtered off and dried, yielding 3.16 g of (±)-2-[hexahydro-1-(phenylmethyl)-1H-azepin-4-yl]-1H-imidazo[4,5-b]pyridine (compound 69). poured out on K2CO3 solid and ice washed with K2CO3 10% extracted with DCM The aqueous layer was washed with DCM The organic layer was dried filtered was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 94/6/0.5) The pure fractions were collected the solvent was evaporated Part of this fraction (6 g) was crystallized from DIPE and 2-propanone The precipitate was filtered off dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of hexahydro-1-(phenylmethyl)-4H-azepin-4-one (0.2 mol) and 4-toluene-sulfonylmethyl isocyanide (0.25 mol) in DMF (200 ml) was stirred at 0° C. A solution of potassium tert-butoxide (0.4 mol) in a mixture of 2-methyl-2-propanol (200 ml) and 1,2-dimethoxyethane (200 ml) was added dropwise at 0° C. The mixture was allowed to reach room temperature and stirring was continued for 1 hour. The mixture was stirred in water and this mixture was extracted with DCM. The separated organic layer was dried, filtered and the solvent was evaporated, yielding 48 g of (±)-hexahydro-1-(phenylmethyl)-1H-azepine-4-carbonitrile (intermediate 1). was added dropwise at 0° C to reach room temperature stirring this mixture was extracted with DCM The separated organic layer was dried filtered the solvent was evaporated