1-(aminomethyl)cyclopentan-1-amine

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

実験手順: 3.35 g of 1-(aminomethyl)cyclopentanamine are solubilized in 20 mL of water, cooled beforehand in an ice bath. 3.52 g of BrCN are added and the mixture is then stirred for 3 h at RT. The solvent is evaporated. 5.67 g (yield=88%) of 1,3-diazaspiro[4.4]non-2-en-2-amine are obtained as a brown oil. cooled beforehand in an ice bath The solvent is evaporated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of crude 1-aminomethyl-cyclopentylamine (Intermediate J) (80 mg, 0.70 mmol) in propan-2-ol (1.0 ml) is added to a suspension of 1-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-2-methyl-isothiourea (Intermediate A) (208 mg, 0.54 mmol) in propan-2-ol (1.08 ml) and heated at 70° C. for 2 days. After cooling to room temperature, the reaction mixture is filtered under vacuum, and the solid is rinsed with MeOH. The filtrate is concentrated in vacuo to afford a bright yellow residue which is loaded onto a SCX-2 cartridge and eluted with 33% NH3 (4 drops) in MeOH (5 ml×2). The methanolic ammonia fractions are combined and concentrated in vacuo. Purification using mass directed preparative LCMS eluting with 95% Water+0.1% NH3: 5% Acetonitrile to affords the title compound; [M+H]+ 310. After cooling to room temperature the reaction mixture is filtered under vacuum the solid is rinsed with MeOH The filtrate is concentrated in vacuo to afford a bright yellow residue which eluted with 33% NH3 (4 drops) in MeOH (5 ml×2) concentrated in vacuo Purification eluting with 95% Water+0.1% NH3

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of crude 1-aminomethyl-cyclopentylamine (Intermediate J) (80 mg, 0.70 mmol) in propan-2-ol (1.0 ml) is added to a suspension of 1-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-2-methyl-isothiourea (Intermediate A) (208 mg, 0.54 mmol) in propan-2-ol (1.08 ml) and heated at 70° C. for 2 days. After cooling to room temperature, the reaction mixture is filtered under vacuum, and the solid is rinsed with MeOH. The filtrate is concentrated in vacuo to afford a bright yellow residue which is loaded onto a SCX-2 cartridge and eluted with 33% NH3 (4 drops) in MeOH (5 ml×2). The methanolic ammonia fractions are combined and concentrated in vacuo. Purification using mass directed preparative LCMS eluting with 95% Water+0.1% NH3: 5% Acetonitrile to affords the title compound; [M+H]+ 310. After cooling to room temperature the reaction mixture is filtered under vacuum the solid is rinsed with MeOH The filtrate is concentrated in vacuo to afford a bright yellow residue which eluted with 33% NH3 (4 drops) in MeOH (5 ml×2) concentrated in vacuo Purification eluting with 95% Water+0.1% NH3

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of crude 1-aminomethyl-cyclopentylamine (Intermediate J) (80 mg, 0.70 mmol) in propan-2-ol (1.0 ml) is added to a suspension of 1-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-2-methyl-isothiourea (Intermediate A) (208 mg, 0.54 mmol) in propan-2-ol (1.08 ml) and heated at 70° C. for 2 days. After cooling to room temperature, the reaction mixture is filtered under vacuum, and the solid is rinsed with MeOH. The filtrate is concentrated in vacuo to afford a bright yellow residue which is loaded onto a SCX-2 cartridge and eluted with 33% NH3 (4 drops) in MeOH (5 ml×2). The methanolic ammonia fractions are combined and concentrated in vacuo. Purification using mass directed preparative LCMS eluting with 95% Water+0.1% NH3: 5% Acetonitrile to affords the title compound; [M+H]+ 310. After cooling to room temperature the reaction mixture is filtered under vacuum the solid is rinsed with MeOH The filtrate is concentrated in vacuo to afford a bright yellow residue which eluted with 33% NH3 (4 drops) in MeOH (5 ml×2) concentrated in vacuo Purification eluting with 95% Water+0.1% NH3

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of crude 1-aminomethyl-cyclopentylamine (Intermediate J) (80 mg, 0.70 mmol) in propan-2-ol (1.0 ml) is added to a suspension of 1-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-2-methyl-isothiourea (Intermediate A) (208 mg, 0.54 mmol) in propan-2-ol (1.08 ml) and heated at 70° C. for 2 days. After cooling to room temperature, the reaction mixture is filtered under vacuum, and the solid is rinsed with MeOH. The filtrate is concentrated in vacuo to afford a bright yellow residue which is loaded onto a SCX-2 cartridge and eluted with 33% NH3 (4 drops) in MeOH (5 ml×2). The methanolic ammonia fractions are combined and concentrated in vacuo. Purification using mass directed preparative LCMS eluting with 95% Water+0.1% NH3: 5% Acetonitrile to affords the title compound; [M+H]+ 310. After cooling to room temperature the reaction mixture is filtered under vacuum the solid is rinsed with MeOH The filtrate is concentrated in vacuo to afford a bright yellow residue which eluted with 33% NH3 (4 drops) in MeOH (5 ml×2) concentrated in vacuo Purification eluting with 95% Water+0.1% NH3

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

実験手順: 2-Methylpyrazolo[1,5-a]pyrimidine-6-carboxylic acid (0.31 g) was suspended in tetrahydrofuran (7 ml), and N,N-dimethylformamide (0.04 ml) was added thereto. A solution of oxalyl chloride (200 μl) in tetrahydrofuran (0.8 ml) was added dropwise thereto with ice cooling, and the mixture was stirred for 1 hour at the same temperature and then stirred for 2 hours at room temperature. Potassium carbonate (0.54 g) was added thereto at −60° C. or less, and then a solution of 1-(aminomethyl)cyclopentylamine (0.22 g) in tetrahydrofuran (0.8 ml) was added dropwise thereto. The mixture was stirred for 30 minutes at −60° C. or less and then stirred for 22 hours at room temperature. Water (6 ml) was added thereto on an ice bath, and the reaction mixture was adjusted to pH 2 by 6 N hydrochloric acid. The reaction mixture was washed with chloroform, and the aqueous phase was adjusted to pH 12 by 5 N sodium hydroxide solution and extracted with chloroform. The resulting product was washed with a saturated saline solution and then dried over sodium sulfate anhydrous. The product was concentrated under reduced pressure to give the title compound (57 mg, Y.:12%). stirred for 2 hours at room temperature The mixture was stirred for 30 minutes at −60° C. or less stirred for 22 hours at room temperature The reaction mixture was washed with chloroform extracted with chloroform The resulting product was washed with a saturated saline solution dried over sodium sulfate anhydrous The product was concentrated under reduced pressure