Cl[C:2](=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[C:10]([C:14]1[O:18][C:17]([C:19]2[C:20]([NH2:37])=[N:21][CH:22]=[C:23]([C:25]3[N:29]([CH3:30])[N:28]=[C:27]([CH:31]4[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]4)[N:26]=3)[N:24]=2)=[N:16][N:15]=1)([CH3:13])([CH3:12])[CH3:11].C(N(CC)CC)C>C(Cl)Cl>[NH2:37][C:20]1[N:21]=[CH:22][C:23]([C:25]2[N:29]([CH3:30])[N:28]=[C:27]([CH:31]3[CH2:36][CH2:35][N:34]([C:2](=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:33][CH2:32]3)[N:26]=2)=[N:24][C:19]=1[C:17]1[O:18][C:14]([C:10]([CH3:13])([CH3:11])[CH3:12])=[N:15][N:16]=1Ethyl 3-chloro-3-oxopropanoate (0.037 mL, 0.29 mmol) was added dropwise to a stirred solution of 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine (100 mg, 0.26 mmol) and triethylamine (0.047 mL, 0.34 mmol) dissolved in CH2Cl2 (1.5 mL) over a period of 2 minutes at 0° C. under nitrogen. The mixture was stirred at 0° C. for 10 minutes then allowed to warm to room temperature and stirred for 1 hour. The mixture was evaporated, dissolved in DMF; a white solid was filtered off and the filtrate was purified by preparative HPLC using a Waters X-Terra reverse-phase column eluting with a mixture of water (containing 0.2% ammonium carbonate) and acetonitrile to afford ethyl 3-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-oxopropanoate (80 mg, 61.7%) as a yellow solid. This material was suspended in THF (2 mL). 2N Sodium hydroxide (0.235 mL, 0.47 mmol) and water (0.5 ml) were added. The mixture was stirred at room temperature overnight. 2N Hydrochloric acid (230 μL) was added to the mixture. The solvents were evaporated. The residue was diluted with CH2Cl2 (30 mL) and water (5 mL). The organic phase was washed with brine and dried over MgSO4. The solvents were evaporated. The resulting foam was triturated in ether. The resulting yellow solid was filtered, dried, triturated in acetonitrile (3 mL). The yellow solid was collected by filtration, dried at 40° C. to afford the title compound (50 mg, 68%) as a yellow solid.
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