Hydrochloric Acid → HCID 178479249, Verbindung

HRID 2204490Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2204490
C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@@H:11]([C:14]([NH:16][NH:17][C:18]2[N:19]=[C:20]3[CH:26]=[CH:25][N:24](S(C4C=CC(C)=CC=4)(=O)=O)[C:21]3=[N:22][CH:23]=2)=O)[CH2:10][CH2:9]1)(C)(C)C.C(OC(N[C@@H]1CC[C@H](C(O)=O)CC1)=O)(C)(C)C.O=S(Cl)[Cl:57].C([O-])([O-])=O.[Na+].[Na+].Cl>CO.O1CCOCC1>[ClH:57].[C:14]1([C@@H:11]2[CH2:12][CH2:13][C@H:8]([NH2:7])[CH2:9][CH2:10]2)[N:19]2[C:20]3[CH:26]=[CH:25][NH:24][C:21]=3[N:22]=[CH:23][C:18]2=[N:17][N:16]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 178427353HCID 178427353, VerbindungHCID 178453971HCID 178453971, Verbindung

Produkt 1

HCID 178479249HCID 178479249, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A round-bottomed flask was charged with cis-tert-butyl-4-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclohexylcarbamate (0.415 g, 0.785 mmol, prepared using A from cis-4-(tert-butoxycarbonylamino)cyclohexanecarboxylic acid [AMRI] and Preparation #9), 1,4-dioxane (9 mL) and SOCl2 (0.115 mL, 1.57 mmol). The resulting mixture was heated at about 90° C. for about 1 h and then allowed to cool to ambient temperature. To the reaction mixture was added aqueous Na2CO3 (5 N, 7.85 mL, 15.7 mmol) and the reaction mixture was heated at about 90° C. for about 5 h. MeOH (5 mL) was added to the reaction mixture and the resulting mixture was heated at about 90° C. for about 16 h and then allowed to cool to ambient temperature. The layers were separated and the organic layer was concentrated under reduced pressure. To the residue was added 1,4-dioxane (10 mL) followed by HCl (4 M in 1,4-dioxane, 5 mL, 20.0 mmol). The resulting suspension was heated at about 60° C. for about 1 h and then allowed to cool to ambient temperature. The solid was collected by vacuum filtration, washed first with 1,4-dioxane (1 mL) then Et2O (50 mL) to yield the crude product cis-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclohexanamine hydrochloride (0.42 g, 98%, 84% purity). A portion of the crude HCl salt (0.075 g) was further purified by RP-HPLC (Table 2, Method g) to give cis-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclohexanamine (0.044 g) with 3 equiv NH4OAc as an excipient. LC/MS (Table 2, Method a) Rt=0.92 min; MS m/z: 257 (M+H)+.

Aufarbeitung

  1. customprepared
  2. temperatureto cool to ambient temperature
  3. temperaturethe reaction mixture was heated at about 90° C. for about 5 h
  4. temperaturethe resulting mixture was heated at about 90° C. for about 16 h
  5. temperatureto cool to ambient temperature
  6. customThe layers were separated
  7. concentrationthe organic layer was concentrated under reduced pressure
  8. additionTo the residue was added 1,4-dioxane (10 mL)
  9. temperatureThe resulting suspension was heated at about 60° C. for about 1 h
  10. temperatureto cool to ambient temperature
  11. filtrationThe solid was collected by vacuum filtration
  12. washwashed first with 1,4-dioxane (1 mL)

Quellen und Nachweise

ORD-Eintrag
ord-55a5788bdd2c438bbb57ba3078d04d41
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365579B2

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