Diisopropylethylamine → (R)-tert-butyl 3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate

To a solution of (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride (5 g, 14.7 mmol) in DCM (78 mL) was added DIEA (7.7 mL, 44.3 mmol) and stirred at ambient temperature for about 10 min followed by the addition of (R)-N-Boc-piperidine-3-carboxylic acid (3.38 g, 14.7 mmol, CNH-Technologies) and HATU (5.61 g, 14.7 mmol). The mixture was stirred for about 1 h at ambient temperature and to it was added water (30 mL) and the layers were separated. The organic layer was washed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to afford crude (R)-tert-butyl 3-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methylcarbamoyl)piperidine-1-carboxylate (7.58 g, 94%): LC/MS (Table 1, Method b) Rt=2.30 min; MS m/z: 514 (M+H)+.

1. stirringThe mixture was stirred for about 1 h at ambient temperature and to it
2. customthe layers were separated
3. washThe organic layer was washed with saturated aqueous NaHCO3 (30 mL) and brine (30 mL)
4. dry with materialdried over anhydrous MgSO4
5. filtrationfiltered
6. customThe crude material was purified by silica gel chromatography
7. washeluting with a gradient of 0-5% MeOH in DCM

ORDレコード

ord-910db809217f4e2ab1be71012c4890a7

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08426411B2