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

HRID 2203985Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2203985
[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]

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 1519426(S)-3-N-Boc-aminomethyl pyrrolidineHCID 18373917Acetonitrile--water (1/1)HCID 60205321N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide

Produkt 1

HCID 86652143(R)-tert-butyl (1-(5-bromo-3-isobutyramido-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-yl)methylcarbamateAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 2631-ButanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

(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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-912a275ff65a43fbb891bb061ab0604b
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365568B2

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