Triethylamine → (R)-tert-butyl 1-(5-chloro-3-(3-methylbutanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Temperature

0 °C

Triethylamine (522 μL, 3.83 mmol) was added to an aliquot of (R)-tert-butyl 1-(3-amino-5-chloro-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (200 mg, 0.547 mmol) in NMP (3 mL) at 0° C. under N2 atmosphere. The mixture was then treated dropwise with 3-methylbutanoyl chloride (231 mg, 1.91 mmol) and stirred at 0° C. After 1 hour, the reaction mixture was diluted with CH2Cl2 (4 mL), and 2M LiOH.H2O (3 mL) was added. The resulting mixture was stirred at room temperature for 18 hours. The mixture was then diluted with additional CH2Cl2 (50 mL) and washed with water (3×10 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by reverse phase chromatography (Biotage SP4, C-18 40M+, 15-85% CH3CN/water, 40 CV) to provide (R)-tert-butyl 1-(5-chloro-3-(3-methylbutanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (130 mg, 53% yield) as a solid.

1. additionwas added
2. stirringThe resulting mixture was stirred at room temperature for 18 hours
3. washwashed with water (3×10 mL)
4. customThe organic layer was separated
5. dry with materialdried (MgSO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by reverse phase chromatography (Biotage SP4

ORD record

ord-7470c1b60e494260ad27d63c83b0980c

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08758830B2