Diisopropylethylamine → (R)-tert-butyl (1-(5-bromo-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)methylcarbamate

HRID 2203985Notes

Reaction equation

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

Participants

Conditions

Temperature: 160 °C

Procedure

(S)-tert-Butyl pyrrolidin-3-ylmethylcarbamate (505 mg, 2.52 mmol) was added to a suspension of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide (252 mg, 0.84 mmol) and N,N-diisopropylethylamine (326 mg, 0.439 mL, 2.52 mmol) in n-BuOH (2.5 mL) The resulting mixture was heated in a sealed tube under nitrogen at 160° C. for 18 hours. The cooled mixture was diluted with water and extracted with EtOAc (3×20 mL). The combined organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated to an oil and purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 20-85% CH3CN/water, 25CV) to give (R)-tert-butyl(1-(5-bromo-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)methylcarbamate (245 mg, 61% yield) as a solid. LCMS (APCI+) m/z 480.1, 482.1 (M+H)+, Retention time=3.66 minutes.

Workup

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

Sources & evidence

ORD record: ord-912a275ff65a43fbb891bb061ab0604b
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365568B2

Reaction notes

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