Dichloromethane → (S)-N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide hydrochloride

HRID 1923936Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1923936
[Br:1][C:2]1[C:3]([N:17]2[CH2:21][CH2:20][C@@H:19]([NH:22]C(=O)OC(C)(C)C)[CH2:18]2)=[C:4]2[C:10]([NH:11][C:12](=[O:16])[C@@H:13]([OH:15])[CH3:14])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.C(O)(C(F)(F)F)=O.C(Cl)[Cl:38]>>[ClH:38].[NH2:22][C@@H:19]1[CH2:20][CH2:21][N:17]([C:3]2[C:2]([Br:1])=[CH:7][N:6]=[C:5]3[NH:8][CH:9]=[C:10]([NH:11][C:12](=[O:16])[C@@H:13]([OH:15])[CH3:14])[C:4]=23)[CH2:18]1

Komponenten

4

Edukt 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 60205673tert-butyl (R)-1-(5-bromo-3-((S)-2-hydroxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate

Produkt 1

HCID 60205674(S)-N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide hydrochlorideAusbeute 58 %

Versuchsvorschrift

tert-Butyl (R)-1-(5-bromo-3-((S)-2-hydroxypropanamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)pyrrolidin-3-ylcarbamate (0.040 g, 0.085 mmol) was placed in DCM (3 mL) at room temperature. TFA (1 mL) was then added, and the reaction was stirred at room temperature for 1 hour and concentrated to dryness. The resulting residue was then purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 0-50% CH3CN/water). The resulting product was next dissolved in minimal DCM (with MeOH to aid solubility) and added to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether and dried to give (S)-N-(4-((R)-3-aminopyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-hydroxypropanamide hydrochloride (0.022 g, 58% yield). 1H NMR (400 MHz, D2O) δ 8.16 (s, 1H), 7.50 (s, 1H), 4.32-4.30 (q, 1H), 4.03-4.00 (m, 1H), 3.89-3.84 (m, 1H), 3.66-3.63 (m, 1H), 3.59-3.55 (m, 1H), 3.48-3.46 (m, 1H), 2.42-2.39 (m, 1H), 2.07-2.04 (m, 1H), 1.34-1.32 (d, 3H); LCMS (APCI+) m/z 368, 370 (M+H)+.

Aufarbeitung

  1. concentrationconcentrated to dryness
  2. customThe resulting residue was then purified by reverse phase chromatography (Biotage SP4
  3. dissolutionThe resulting product was next dissolved in minimal DCM (with MeOH to aid solubility)
  4. additionadded to a stirring solution of 1M HCl in ether
  5. filtrationThe resulting solid was filtered
  6. washwashed with ether
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-8eacad6ca8b54eacb37ce6eebac8b245
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178131B2

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