[CH3:1][C:2]1([CH3:32])[C@@H:5]([C:6]2[N:10]3[C:11]4[CH:17]=[CH:16][N:15]([S:18]([C:21]5[CH:27]=[CH:26][C:24]([CH3:25])=[CH:23][CH:22]=5)(=[O:20])=[O:19])[C:12]=4[N:13]=[CH:14][C:9]3=[N:8][N:7]=2)[CH2:4][C@H:3]1[NH:28]C(=O)C.C(N[C@@H]1C[C@H](C(O)=O)C1(C)C)(=O)C.CCN(C(C)C)C(C)C.Cl>O1CCOCC1.C(Cl)CCl>[CH3:1][C:2]1([CH3:32])[C@@H:5]([C:6]2[N:10]3[C:11]4[CH:17]=[CH:16][N:15]([S:18]([C:21]5[CH:22]=[CH:23][C:24]([CH3:25])=[CH:26][CH:27]=5)(=[O:20])=[O:19])[C:12]=4[N:13]=[CH:14][C:9]3=[N:8][N:7]=2)[CH2:4][C@H:3]1[NH2:28]To a solution of N-((1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutyl)acetamide (2.20 g, 4.86 mmol, prepared using A from Preparation #9 and (1S,3R)-3-acetamido-2,2-dimethylcyclobutanecarboxylic acid [prepared as described in Tetrahedron: Asymmetry 2008, 19, 302-308] with EDC, C with DIEA) in 1,4-dioxane (30 mL) was added 6 N aqueous HCl (32.4 mL, 194 mmol). The reaction was heated at about 100° C. for about 16 h. The reaction was allowed to cool to ambient temperature and was partitioned between EtOAc (500 mL) and aqueous NaHCO3 (500 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give (1R,3S)-2,2-dimethyl-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclobutanamine (1.56 g, 78%) as a tan solid: LC/MS (Table 2, Method a) Rt=1.60 min; MS m/z: 411 (M+H)+.
Loading…