Hydrochloric Acid → HCID 46215813, compound

Participants

Reaction Conditions

Reaction Steps

To a 5-mL microwave vial was added 6-chloro-N4-methyl-N4-phenyl-2,4-pyrimidinediamine (61 mg, 0.260 mmol), 1,1-dimethylethyl 3-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate (218 mg, 0.390 mmol), K2CO3 (0.130 mL, 0.260 mmol), PdCl2(dppf).CH2Cl2 adduct (212 mg, 0.260 mmol) and 1,4-dioxane (3 mL). The vial was capped and stirred for 10 minutes at 150° C. in a microwave reactor. The reaction mixture was concentrated in vacuo, and the residue was dissolved in EtOAc (50 mL) and water (20 mL). The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organics were dried with Na2SO4, then filtered. The filtrate was concentrated, and dissolved in dioxane (10 mL) and CH3OH (1 mL), and HCl (0.5 mL, 2 mmol) in dioxane was added. The reaction was stirred overnight at 40° C. At this time, LCMS analysis indicated complete conversion to the desired product. The reaction mixture was concentrated, and the residue was dissolved in DMSO and purified by RP-HPLC (15-35% CH3CN in H2O; 0.1% TFA). The fractions containing the product were combined, concentrated to remove the CH3CN, basified (NaHCO3, pH paper) and extracted into EtOAc. The organic layer was dried and concentrated to afford the title compound as a yellow solid (19 mg). LC-MS (ES) m/z=332 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 3.46 (s, 3H), 5.38-5.52 (m, 2H), 5.94-6.15 (m, 1H), 6.25-7.00 (bs, 1H), 7.12-7.27 (m, 1H), 7.34-7.46 (m, 4H), 7.47-7.57 (m, 2H), 7.58-7.66 (m, 1H), 7.67-7.78 (m, 1H), 11.40-11.77 (m, 1H).

Provenance & Evidence