Sodium Hydroxide → (+/-) N-(3-{[2-(10-Aza-tricyclo[6.3.1.02.7]dodeca-2(7),3,5-trien-4-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino]-methyl}-pyridin-2-yl)-methanesulfonamide

Participants

Reaction Conditions

Reaction Steps

A solution 3 and tetrahydrofuran (2.00 mL) was treated with three crystals of benzyl triethyl ammonium chloride and 40% aqueous NaOH (2.00 mL), and the resultant bi-phasic reaction was heated to 70° C. under nitrogen. After sixteen hours, the mixture was allowed to cool to 25° C. The organic phase was collected and the aqueous layer was washed with EtOAc. The combined organic phases were dried over MgSO4, concentrated under reduced pressure, and purified over silica (92:8:0.8 CHCl3:CH3OH: NH4OH) to provide 32 g of 4 as a yellow foam). The yellow foam was dissolved in a minimum amount of CH2Cl2 at ° C., and 15 μL (0.0600 mmol) of 4.0 M HCl in 1,4-dioxane was slowly added. The resultant white slurry was stirred under a gentle flow of nitrogen for one hour and filtered to provide the hydrochloride salt from of 4 as a white solid (25 mg, 0.0474 mmol, 38%). C24H26F3N7O2S HPLC r.t.=5.10 min.; LC/MS (Method F) m/z 534.4 (MH+).

Provenance & Evidence