1-methyl-2,3-dihydropyridin-6-one

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.106 g, 0.602 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.205 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.090 mmol), N,N-dicyclohexylmethylamine (0.129 mL, 0.663 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one (0.0153 g, 12.32% yield) as a tan solid. [M+1]=207.1. Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium bis(trimethylsilyl)amide (11 mL of 1 M solution in THF) cooled to −78° C. under nitrogen was added dropwise a solution of tosylmethyl isocyanide (1.9 g, 10 mmol) in THF (45 mL). After stirring for 40 minutes at −78° C., a solution of 1-methyl-5,6-dihydro-1H-pyridin-2-one (1.1 g, 10 mmol) in THF (10 mL) was added and the mixture was stirred at room temperature for overnight. The reaction was concentrated and the residue was partitioned between water (150 mL) and dichloromethane (150 mL). The aqueous was extracted with dichloromethane (3×). The combined organic layers were concentrated and dried under high vacuum. The resulting foam was recrystallized from dichloromethane to give 633 mg (42%) of 5-methyl-2,5,6,7-tetrahydro-pyrrolo[3,4-c]pyridin-4-one as a light yellow solid. the mixture was stirred at room temperature for overnight The reaction was concentrated the residue was partitioned between water (150 mL) and dichloromethane (150 mL) The aqueous was extracted with dichloromethane (3×) The combined organic layers were concentrated dried under high vacuum The resulting foam was recrystallized from dichloromethane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium bis(trimethylsilyl)amide (11 mL of 1 M solution in THF) cooled to −78° C. under nitrogen was added dropwise a solution of tosylmethyl isocyanide (1.9 g, 10 mmol) in THF (45 mL). After stirring for 40 minutes at −78° C., a solution of 1-methyl-5,6-dihydro-1H-pyridin-2-one (1.1 g, 10 mmol) in THF (10 mL) was added and the mixture was stirred at room temperature for overnight. The reaction was concentrated and the residue was partitioned between water (150 mL) and dichloromethane (150 mL). The aqueous was extracted with dichloromethane (3×). The combined organic layers were concentrated and dried under high vacuum. The resulting foam was recrystallized from dichloromethane to give 633 mg (42%) of 5-methyl-2,5,6,7-tetrahydro-pyrrolo[3,4-c]pyridin-4-one as a light yellow solid. the mixture was stirred at room temperature for overnight The reaction was concentrated the residue was partitioned between water (150 mL) and dichloromethane (150 mL) The aqueous was extracted with dichloromethane (3×) The combined organic layers were concentrated dried under high vacuum The resulting foam was recrystallized from dichloromethane

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.10 g, 0.60 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.20 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.09 mmol), N,N-dicyclohexylmethylamine (0.13 mL, 0.66 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one as a tan solid. MS (ESI, pos. ion) m/z: 207.1 (M+1). Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.106 g, 0.602 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.205 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.090 mmol), N,N-dicyclohexylmethylamine (0.129 mL, 0.663 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one (0.0153 g, 12.32% yield) as a tan solid. [M+1]=207.1. Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.106 g, 0.602 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.205 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.090 mmol), N,N-dicyclohexylmethylamine (0.129 mL, 0.663 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one (0.0153 g, 12.32% yield) as a tan solid. [M+1]=207.1. Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.106 g, 0.602 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.205 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.090 mmol), N,N-dicyclohexylmethylamine (0.129 mL, 0.663 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one (0.0153 g, 12.32% yield) as a tan solid. [M+1]=207.1. Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium bis(trimethylsilyl)amide (11 mL of 1 M solution in THF) cooled to −78° C. under nitrogen was added dropwise a solution of tosylmethyl isocyanide (1.9 g, 10 mmol) in THF (45 mL). After stirring for 40 minutes at −78° C., a solution of 1-methyl-5,6-dihydro-1H-pyridin-2-one (1.1 g, 10 mmol) in THF (10 mL) was added and the mixture was stirred at room temperature for overnight. The reaction was concentrated and the residue was partitioned between water (150 mL) and dichloromethane (150 mL). The aqueous was extracted with dichloromethane (3×). The combined organic layers were concentrated and dried under high vacuum. The resulting foam was recrystallized from dichloromethane to give 633 mg (42%) of 5-methyl-2,5,6,7-tetrahydro-pyrrolo[3,4-c]pyridin-4-one as a light yellow solid. the mixture was stirred at room temperature for overnight The reaction was concentrated the residue was partitioned between water (150 mL) and dichloromethane (150 mL) The aqueous was extracted with dichloromethane (3×) The combined organic layers were concentrated dried under high vacuum The resulting foam was recrystallized from dichloromethane

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.10 g, 0.60 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.20 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.09 mmol), N,N-dicyclohexylmethylamine (0.13 mL, 0.66 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one as a tan solid. MS (ESI, pos. ion) m/z: 207.1 (M+1). Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a sealed tube were placed 3-bromo-2-fluoropyridine (0.106 g, 0.602 mmol), 1-methyl-5,6-dihydropyridin-2(1H)-one (0.134 g, 1.205 mmol), bis(tri-tert-butylphosphine)palladium (0) (0.046 g, 0.090 mmol), N,N-dicyclohexylmethylamine (0.129 mL, 0.663 mmol), and 1,4-dioxane (0.5 mL). After the mixture was degassed for 5 min, the reaction was heated at 100° C. for 3 h. The cooled reaction was concentrated in vacuo, and the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc) to give 4-(2-fluoropyridin-3-yl)-1-methyl-5,6-dihydropyridin-2(1H)-one (0.0153 g, 12.32% yield) as a tan solid. [M+1]=207.1. Into a sealed tube were placed After the mixture was degassed for 5 min The cooled reaction was concentrated in vacuo the brown residue was directly purified via flash column chromatography (20% EtOAc/Hexanes to 100% EtOAc)