(3R)-3-Aminopiperidine, 3-BOC protected → HCID 67045837, compound

HRID 1034816Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:2]1.[Br:15][C:16]1[C:17](F)=[C:18]2[C:24]([NH:25][C:26]([C:28]3([O:31][CH3:32])[CH2:30][CH2:29]3)=[O:27])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1.CC#N.O>CCCCO.O>[Br:15][C:16]1[C:17]([N:1]2[CH2:6][CH2:5][CH2:4][C@@H:3]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:2]2)=[C:18]2[C:24]([NH:25][C:26]([C:28]3([O:31][CH3:32])[CH2:30][CH2:29]3)=[O:27])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1

Participants

Conditions

Temperature: 160 °C

Procedure

(R)-tert-Butyl piperidin-3-ylcarbamate (366 mg, 1.83 mmol) was added to a suspension of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-1-methoxycyclopropanecarboxamide (200 mg, 0.61 mmol) in n-BuOH (3 mL). The resulting mixture was heated in a sealed tube at 160° C. for 24 hours. The cooled mixture was diluted with water (40 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were dried over MgSO4 and filtered, and the filtrate was concentrated. The residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-85% CH3CN/water, 25 CV) to give (R)-tert-butyl 1-(5-bromo-3-(1-methoxycyclopropanecarboxamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (103 mg, 33% yield) as a solid. LCMS (APCI+) m/z 510 (M+2H)+, Retention time=3.84 minutes.

Workup

extractionextracted with EtOAc (3×20 mL)
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationthe filtrate was concentrated
customThe residue was purified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record: ord-9af0c4834d454986b019e62643b83241
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08545897B2

Reaction notes

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