Dichloromethane → tert-butyl 4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)-bicyclo[2.2.2]octan-1-ylcarbamate

A round bottom flask was charged with 2-hydrazinyl-5-tosyl-5H-pyrrolo[2,3-b]pyrazine (3.75 g, 11.1 mmol, Preparation #9), 4-(tert-butoxycarbonylamino)bicyclo[2.2.2]octane-1-carboxylic acid (3.0 g, 11 mmol, Prime Organics), HATU (4.23 g, 11.1 mmol), TEA (6.2 mL, 44 mmol), and DCM (65 mL). The reaction mixture was stirred at ambient temperature for about 16 h. The reaction mixture was diluted with water (30 mL) and the layers were separated. The reaction mixture was filtered through Celite® and washed with DCM (60 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc in DCM to afford tert-butyl 4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)bicyclo[2.2.2]octan-1-ylcarbamate as a brown amorphous solid (5.38 g, 87%): LC/MS (Table 2, Method a) Rt=2.40 min; MS m/z 555 (M+H)+.

1. customthe layers were separated
2. filtrationThe reaction mixture was filtered through Celite®
3. washwashed with DCM (60 mL)
4. washThe organic layer was washed with water (3×50 mL)
5. dry with materialdried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude material was purified by silica gel chromatography
9. washeluting with a gradient of 0-100% EtOAc in DCM

ORDレコード

ord-6c7f1aebc20043d188cd2a5ebc66f7d6

出典データセット

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08962629B2