Diisopropylethylamine → HCID 67045507, compound

HRID 408285Notes

Reaction equation

[Br:1][C:2]1[C:3](F)=[C:4]2[C:10]([NH:11][C:12](=[O:18])[CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[NH:20]1[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[CH2:21]1.C(N(C(C)C)C(C)C)C>CCCCO>[Br:1][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][CH2:23][C@@H:22]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:21]2)=[C:4]2[C:10]([NH:11][C:12](=[O:18])[CH:13]([CH2:16][CH3:17])[CH2:14][CH3:15])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-ethylbutanamide (225 mg, 0.686 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (412 mg, 2.06 mmol), and N-ethyl-N-isopropylpropan-2-amine (239 μL, 1.37 mmol) in n-BuOH (5 mL) was purged under N2 and stirred at 160° C. in a sealed tube for 16 hours. The solvent was then removed in vacuo, and the liquid residue was purified by C-18 reverse phase column chromatography (Biotage Flash 25M+; C-18) on Biotage SP4 unit eluting with a gradient of 15-90% CH3CN/water (25 CV) to provide (R)-tert-butyl 1-(5-bromo-3-(2-ethylbutanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (201 mg, 58% yield) as a solid. LCMS (APCI+) m/z 508, 510 (M+H)+, Retention time=4.15 minutes (Method 2).

Workup

customwas purged under N2
customThe solvent was then removed in vacuo
customthe liquid residue was purified by C-18 reverse phase column chromatography (Biotage Flash 25M+; C-18) on Biotage SP4 unit
washeluting with a gradient of 15-90% CH3CN/water (25 CV)

Sources & evidence

ORD record: ord-b10ae654f87f44edb857c4a6ccd5904a
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08758830B2

Reaction notes

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