Water → (S)-(1-(6-(1-(6-(piperazin-1-yl)pyridin-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)pyrazin-2-yl)pyrrolidin-2-yl)methanol dihydrochloride

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A mixture of 3-5 eq. of (S)-pyrrolidin-2-ylmethanol, 1 eq. of tert-butyl 4-(6-(6-(6-chloropyrazin-2-yl)-1H-pyrazolo[4,3-c]pyridin-1-yl)pyridin-2-yl)piperazine-1-carboxylate, 6-10 eq of cesium fluoride in DMSO was heated at 105° C. for 12-24 hours. The mixture was mixed with water and extracted with ethyl acetate. The organic extracts were washed with water, brine, dried over sodium sulfate and concentrated in vacuum. The crude products were purified on a silica gel column eluting with gradient of ethyl acetate in heptane or DCM. The Boc group was deprotected with 4 M HCl in dioxane in methanol. The crude product was collected by filtration, dissolved in water and lyophilized to give 280. 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H), 9.31-9.19 (m, 2H), 9.10 (s, 1H), 8.80 (s, 1H), 8.73 (s, 1H), 8.19 (s, 1H), 7.89 (t, J=8.1 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 6.97 (d, J=8.5 Hz, 1H), 4.21 (d, J=6.0 Hz, 1H), 3.93 (t, J=5.3 Hz, 4H), 3.58 (m, 1H), 3.49 (m, 2H), 3.22 (d, J=5.4 Hz, 4H), 2.06 (m, 4H). MS (ESI) m/z: 458.3.

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