Hydrochloric Acid → (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

HRID 1969620Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1969620
[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30]C(=O)C)[CH2:4]1)[CH3:2].Cl>O1CCOCC1>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17]([S:20]([C:23]5[CH:24]=[CH:25][C:26]([CH3:27])=[CH:28][CH:29]=5)(=[O:22])=[O:21])[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH2:30])[CH2:4]1)[CH3:2]

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 58557700N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetamide

Produkt 1

HCID 58557840(1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamineAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of N-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl)acetamide (6.0 g, 12.86 mmol, Example #8, Step L) in 1,4-dioxane (78 mL) was added aqueous HCl (6 N, 75 mL, 450 mmol). The reaction mixture was heated at about 95° C. for about 16 h. The reaction was cooled to ambient temperature and the solvent was removed under reduced pressure. The residue was diluted with DCM (50 mL) and washed with saturated aqueous NaHCO3 (100 mL). The aqueous portion was extracted with additional DCM (3×50 mL) and the combined organic layers were dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-100% DCM/MeOH/NH4OH (950:45:5) in DCM to give (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (3.05 g, 56%) as a tan solid: LC/MS (Table 1, Method a) Rt=1.85 min; MS m/z: 425 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction was cooled to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. additionThe residue was diluted with DCM (50 mL)
  4. washwashed with saturated aqueous NaHCO3 (100 mL)
  5. extractionThe aqueous portion was extracted with additional DCM (3×50 mL)
  6. dry with materialthe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe crude material was purified by silica gel chromatography
  9. washeluting with a gradient of 0-100% DCM/MeOH/NH4OH (950:45:5) in DCM

Quellen und Nachweise

ORD-Eintrag
ord-aaf1d910264c4f85a0c11bcbbe5be9d7
Quelldatensatz
uspto-grants-2013_04
Patentnummer
US08426411B2

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