(R)-tert-butyl 1-(5-chloro-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate → (R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide hydrochloride

HRID 408368Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 408368
[Cl:1][C:2]1[C:3]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24]C(=O)OC(C)(C)C)[CH2:19]2)=[C:4]2[C:10]([NH:11][C:12](=[O:17])[C:13]([OH:16])([CH3:15])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1>FC(F)(F)C(O)=O>[ClH:1].[NH2:24][C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:3]2[C:2]([Cl:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:17])[C:13]([OH:16])([CH3:14])[CH3:15])[C:4]=23)[CH2:19]1

Komponenten

3

Edukt 1

HCID 67045520(R)-tert-butyl 1-(5-chloro-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate

Produkt 1

HCID 67045257(R)-N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide hydrochlorideAusbeute 108,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

(R)-tert-Butyl 1-(5-chloro-3-(2-hydroxy-2-methylpropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamate (221 mg, 0.489 mmol) was stirred in trifluoroacetic acid (3 mL) at room temperature for 1.5 hours. The solvent was evaporated in vacuo, and the residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 2-55% CH3CN/water, 25CV). The isolated product was taken up in a minimal volume of methanol and added to a stirred solution of 2N HCl-Et2O. The salt formed was collected by filtration, washed with acetonitrile and dried under vacuum to give (R)—N-(4-(3-aminopiperidin-1-yl)-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxy-2-methylpropanamide hydrochloride (103 mg, 50% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.05 (s, 1H), 7.53 (s, 1H), 3.64-3.48 (m, 2H), 3.53-3.22 (m, 1H), 3.24-3.16 (m, 1H), 3.12-3.04 (m, 1H), 2.12-2.04 (m, 1H), 1.80-1.66 (m, 2H), 1.56-1.44 (m, 1H), 1.38 (s, 3H), 1.35 (s, 3H). LCMS (APCI+) m/z 352.1, 354.1 (M+H)+, Retention time=2.02 minutes.

Aufarbeitung

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by reverse phase chromatography (Biotage SP4
  3. additionadded to a stirred solution of 2N HCl-Et2O
  4. customThe salt formed
  5. filtrationwas collected by filtration
  6. washwashed with acetonitrile
  7. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-7fe87390afcc449b969c7eb3eefbcc6f
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08758830B2

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