[CH3:1][N:2]1[C:6]([CH2:7][C:8]#[N:9])=[CH:5][CH:4]=[N:3]1.[C:10](Cl)(=O)[CH3:11].Cl.Cl.N[C:17]1[CH:18]=[CH:19][C:20]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:31])[CH2:25]2)=[N:21][C:22]=1[NH2:23].C(N(CC)CC)C.C(O)(=O)C>C(O)C>[CH3:1][N:2]1[C:6]([C:7]2([C:8]3[NH:23][C:22]4=[N:21][C:20]([N:24]5[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]6[CH2:36][CH2:35][CH2:34][CH2:33]6)=[O:31])[CH2:25]5)=[CH:19][CH:18]=[C:17]4[N:9]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=[N:3]1To a solution of 2-(1-methyl-1H-pyrazol-5-yl)acetonitrile (14.5 mg, 0.10 mmol) in ethanol (150 μL, 2.6 mmol) was added acetyl chloride (110 μL, 1.5 mmol). The reaction mixture was stirred at room temperature for 16 h. The solvent was removed under a stream of nitrogen. Ethanol (0.5 mL) was added to the residue followed by a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (36 mg, 0.01 mmol) and triethylamine (70 μL, 0.50 mmol) in ethanol (1 mL). Acetic acid (100 μL, 1.75 mmol) was added and the reaction mixture was heated in the microwave for 45 min at 130° C. The solvent was removed under a stream of nitrogen. Ethyl acetate (10 mL) was added to the residue. The solution was washed with aqueous sodium hydroxide (1N, 3 mL), washed with water (3 mL), washed with brine (3 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 420.3; HPLC retention time 1.88 min (Method B).
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