Hydrochloric Acid → HCID 178479249, compound

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence