Hydrochloric Acid → HCID 178479249, compound

HRID 2204490Notes

Reaction equation

HRID 2204490 reaction equation
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

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 24386Thionyl ChlorideHCID 178427353HCID 178427353, compoundHCID 178453971HCID 178453971, compound

Product 1

HCID 178479249HCID 178479249, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-55a5788bdd2c438bbb57ba3078d04d41
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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