Diisopropylethylamine → HCID 67045239, compound

HRID 875820Notes

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.C(N(CC)C(C)C)(C)C.[Br:24][C:25]1[C:26](F)=[C:27]2[C:33]([NH:34][C:35](=[O:40])[C:36]([OH:39])([CH3:38])[CH3:37])=[CH:32][NH:31][C:28]2=[N:29][CH:30]=1.CC#N.O>CCCCO.O>[Br:24][C:25]1[C:26]([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:27]2[C:33]([NH:34][C:35](=[O:40])[C:36]([OH:39])([CH3:38])[CH3:37])=[CH:32][NH:31][C:28]2=[N:29][CH:30]=1

Participants

Conditions

Temperature: 150 °C

Procedure

(R)-tert-Butyl piperidin-3-ylcarbamate (538 mg, 2.69 mmol) and N,N-diisopropylethylamine (347 mg, 0.468 mL, 2.69 mmol) were added to a suspension of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide (283 mg, 0.895 mmol) in n-BuOH (3 mL). The resulting mixture was heated at 150° C. in a sealed tube for 24 hours. The cooled mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic layers were dried over MgSO4 and filtered, and the filtrate concentrated to an oil and purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 15-75% CH3CN/water, 25CV) to give (R)-tert-butyl 1-(5-bromo-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (242 mg, 55% yield) as a solid. LCMS (APCI+) m/z 496.2, 498.2 (M+H)+, Retention time=3.53 minutes.

Workup

extractionextracted with EtOAc (3×20 mL)
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationthe filtrate concentrated to an oil
custompurified by reverse phase chromatography (Biotage SP4

Sources & evidence

ORD record: ord-1dc625d4f3444b1dbced8494a6f58bee
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08981085B2

Reaction notes

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