[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:20]([C:21]4[CH:26]=[CH:25][C:24]([CH2:27][OH:28])=[CH:23][CH:22]=4)=[N:19][CH:18]=[CH:17][N:16]=3)[CH2:11][CH2:10]2)[CH:4]=[N:3]1.C([C:36]1[NH:37][CH:38]=CN=1)(C1NC=CN=1)=O.CN.[O:43]1CCCC1.C(Cl)[Cl:49]>>[ClH:49].[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH2:8][N:9]2[CH2:10][CH2:11][N:12]([C:15]3[C:20]([C:21]4[CH:26]=[CH:25][C:24]([CH2:27][O:28][C:38](=[O:43])[NH:37][CH3:36])=[CH:23][CH:22]=4)=[N:19][CH:18]=[CH:17][N:16]=3)[CH2:13][CH2:14]2)[CH:4]=[N:3]1Dissolve {4-[4-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl-3′-yl]-phenyl}-methanol (200 mg, 0.53 mmol) in DCM (5 mL) at room temperature under nitrogen. Add carbonyl diimidazole (94 mg, 0.58 mmol) and stir for 20 hr. Add a solution of methylamine in tetrahydrofuran (2 M, 2 mL, 4.0 mmol) and stir reaction for 2 hr. at room temperature. Quench reaction with water (10 mL) then extract with DCM (2×10 mL), pass through an IST Phase Separator Frit® and concentrate. Purify by low pH reverse phase HPLC, and form the free base by passing through an SCX-2® ion exchange cartridge washing with methanol then eluting with 3 M ammonia in methanol. Dissolve the oil in acetonitrile and convert to the hydrochloride salt by adding 2 M aq HCl solution. Add water and lyophilize to give the title compound as a yellow powder (28 mg, 12%). MS (ES): m/z=436 [M+H]+
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