2-amino-1,1-diphenylethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazol-5-ylthio)picolinic acid (43.2 mg, 0.0912 mmol) and 2-amino-1,1-diphenylethanol (30.8 mg, 0.144 mmol, described in Synthesis of amines, Example D) in NMP (3 mL) was added HOBT (12.3 mg, 0.0910 mmol), EDAC (27.4 mg, 0.143 mmol) and diisopropylethylamine (0.05 mL, 0.281 mmol). The reaction was stiffed at 23° C. overnight and was purified on Prep HPLC (water/acetonitrile/ammonium acetate) to give the title material (26.7 mgs, 44%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm: 10.51 (1H, s), 8.35-8.42 (2H, m), 7.75 (s, 1H), 7.62 (1H, d, J=1.26 Hz), 7.43 (5H, d, J=7.07 Hz), 7.34 (1H, dd, J=5.31, 2.02 Hz), 7.27 (5H, t, J=7.71 Hz), 7.16 2H, t, J=7.33 Hz), 6.30 (1H, s), 6.03 (1H, s), 4.45 (1H, t, J=5.18 Hz), 4.09 (2H, d, J=5.56 Hz), 3.50 (7H, s), 2.41 (3H, t, J=6.32 Hz), 2.33 (3H, s). LC/MS (M+H)+: 669. HPLC ret. time (Condition E): 1.84 min. HRMS calcd: 669.2430; found: 669.2434. was purified on Prep HPLC (water/acetonitrile/ammonium acetate)

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(2-(pyridine-2-ylamino)thiazol-5-ylthio)picolinic acid (0.063 g, 0.19 mmol) and 2-amino-1,1-diphenylethanol (0.060 g, 0.28 mmol, 1.5 eq, described in Example D) in NMP (3 mL), was added EDAC (0.055 g, 0.28 mmol, 1.5 eq), HOBt (0.026 g, 0.19 mmol, 1 eq) and diisopropylethylamine (0.100 mL, 0.57 mmol, 3 eq). The resulting mixture was stirred at 23° C. for 3.5 h. The mixture was purified on preparative HPLC (ammonium acetate/water/acetonitrile) and freeze dried to give the title compound as a solid (0.024 mg, 24%). The product was converted to the HCl salt by dissolving it in ethyl acetate (2 mL) and tetrahydrofuran (2 mL) and treating the mixture with a solution of HCl (4.0 M in dioxane, 0.011 mL, 0.045 mmol, 1 eq). The mixture was concentrated, then diluted with water and lyophilized to give the HCl salt of the title material (0.029 g) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.10 (2H, d, J=5.56 Hz), 6.30 (1H, s), 7.01 (1H, dd, J=6.69 and 5.43 Hz), 7.11-7.20 (3H, m), 7.28 (4H, t, J=7.71 Hz), 7.37 (1H, dd, J=5.31, 2.02 Hz), 7.42-7.48 (4H, m), 7.66 (1H, d, J=1.52 Hz), 7.79 (1H, ddd, J=9.22, 6.32 and 1.89 Hz), 8.31 (1H, dd, J=5.43 and 1.39 Hz), 8.40 (1H, t, J=4.80 Hz), 8.41 (1H, d, J=4.8 Hz), 11.86 (1H, s). LC/MS (M+H)+: 526. Ret. time: 2.00 (Condition D). HRMS: calcd: 526.1371; found: 526.1387. The mixture was purified on preparative HPLC (ammonium acetate/water/acetonitrile) freeze dried