Potassium Carbonate → N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)pyrrolidine-1-sulfonamide

A round bottom flask was charged with 4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-amine (0.12 g, 0.28 mmol), DIEA (0.48 mL, 2.8 mmol) in DMA (2.75 mL). Pyrrolidine-1-sulfonyl chloride (0.07 g, 0.41 mmol, Matrix) was added dropwise and reaction mixture was stirred at ambient temperature for about 1 h. K2CO3 (0.190 g, 1.37 mmol) was added and the reaction mixture was stirred at ambient temperature for about 16 h. The solvent was removed under reduced pressure. The crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM to give N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)pyrrolidine-1-sulfonamide, which was dissolved in NaOH (1 N aqueous, 1.10 mL, 1.10 mmol) and 1,4-dioxane (1 mL) and heated at about 50° C. for about 1 h. The crude material was purified by preparative reverse phase HPLC (Table 2, Method 1) to give N-(4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)pyrrolidine-1-sulfonamide (0.042 g, 37%) as a white solid: LC/MS (Table 1, Method a) Rt=1.81 min; MS m/z 416 (M+H)+.

1. customreaction mixture
2. stirringthe reaction mixture was stirred at ambient temperature for about 16 h
3. customThe solvent was removed under reduced pressure
4. customThe crude material was purified by flash chromatography on silica gel eluting with a gradient of 0-10% MeOH in DCM

ORDレコード

ord-41cd2d13804b4b4f9ae22ac8742df106

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08426411B2