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

HRID 875905Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 875905
[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>[Br:15][C:16]1[C:17]([N:1]2[CH2:5][CH2:4][C@H:3]([CH2:6][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](=[O:30])[CH:27]([CH3:28])[CH3:29])=[CH:23][NH:22][C:19]2=[N:20][CH:21]=1

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-3d0d548232df4636b8a05d07ed098a1a
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08981085B2

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