[C:1]1([C:7]2[C:14]3[S:13][C:12]([NH2:15])=[N:11][C:10]=3[NH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:16][C:17]1[S:18][C:19]([C:23](Cl)=[O:24])=[C:20]([CH3:22])[N:21]=1.C1(C)C=CC=CC=1.C(O)C(N)(CO)CO>CN(C1C=CN=CC=1)C.C1COCC1>[C:1]1([C:7]2[C:14]3[S:13][C:12]([NH:15][C:23]([C:19]4[S:18][C:17]([Cl:16])=[N:21][C:20]=4[CH3:22])=[O:24])=[N:11][C:10]=3[NH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
To a vial charged with 3-phenyl-1H-pyrazolo[3,4-d]thiazol-5-ylamine (30 mg, 0.139 mmol), PS-DMAP (Argonaut resin, 558 mg, 6 equiv.), and a stirring bar was added THF (2 mL) and 2-chloro-4-methyl-thiazole-5-carbonyl chloride solution in toluene (0.52 M, 1.3 mL, ca. 5 equiv.). The reaction mixture was stirred at 70° C. for 18 hours, then cooled to room temperature and treated with PS-trisamine (Argonaut resin, 674 mg, 20 equiv.) for 2 hours. The resin was filtered, washed with THF and the solvent was evaporated. The resulting crude mixture was treated with MeOH (1 mL) and a 4 N aqueous solution of NaOH (0.25 mL). The reaction mixture was further stirred at room temperature for 2 hours, then a 1 N aqueous solution of HCl was added to adjust the pH to 7, and the mixture was extracted with EtOAc (3×). Purification on silica gel with 0-10% MeOH in CH2Cl2 as eluent provided 11 mg (21% yield) of 2-chloro-4-methyl-thiazole-5-carboxylic acid (3-phenyl-1H-pyrazolo[3,4-d]thiazol-5-yl)-amide as an off-white solid. 1H-NMR (d6-DMSO) δ: 7.75 (d, 2H), 7.54 (t, 2H), 7.39 (t, 1H), 2.65 (s, 3H); HPLC/MS m/z: 376.0 [MH]+.
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