Triethylamine → (R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

HRID 875861Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 875861
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.C(N(CC)CC)C.[NH2:29][C:30]1[C:38]2[C:33](=[N:34][CH:35]=[C:36]([Br:53])[C:37]=2[N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:40]2)[NH:32][CH:31]=1>CC#N.O.O.CN1C(=O)CCC1>[Br:53][C:36]1[C:37]([N:39]2[CH2:44][CH2:43][CH2:42][C@@H:41]([NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:49])[CH3:51])[CH2:40]2)=[C:38]2[C:30]([NH:29][C:4](=[O:6])[CH2:3][C:1]#[N:2])=[CH:31][NH:32][C:33]2=[N:34][CH:35]=1

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 9740Cyanoacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 67045407(R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Produkt 1

HCID 67045531(R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamateAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittelHCID 18373917Acetonitrile--water (1/1)Lösungsmittel

Versuchsvorschrift

2-Cyanoacetic acid (0.332 g, 3.90 mmol), BOP-Cl (0.993 g, 3.90 mmol), and triethylamine (1.02 mL, 7.31 mmol) were added to an NMP solution (2 mL) of (R)-tert-butyl 1-(3-amino-5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.200 g, 0.487 mmol; Example 98, Step A). The reaction was then stirred for 18 hours, then poured into water, and extracted with DCM. The combined organic fractions were dried (MgSO4), filtered, and concentrated to give the crude product, which was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 5-95% CH3CN/water) to give (R)-tert-butyl 1-(5-bromo-3-(2-cyanoacetamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (0.06 g, 26% yield).

Aufarbeitung

  1. extractionextracted with DCM
  2. dry with materialThe combined organic fractions were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified by reverse phase chromatography (Biotage SP4

Quellen und Nachweise

ORD-Eintrag
ord-30c600e090654fd2b7eb2d4afb79c506
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08981085B2

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