Acetic Acid → (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-3-(4-methylpiperazin-1-yl)-1H-indazol-5-yl)benzo[d]thiazol-6-yl)acetic acid

Participants

Reaction Conditions

Reaction Steps

A vial was charged with 5-bromo-1-methyl-3-(4-methylpiperazin-1-yl)-1H-indazole (64.0 mg, 0.208 mmol), bis-pinacolatodiboron (58 mg, 0.23 mmol), PdCl2(dppf).DCM (17 mg, 21 μmol), glacial AcOH (13 μL, 0.23 mmol), KOAc (67 mg, 0.69 mmol), and dioxane (1.6 mL). The reaction was heated to 100° C. for 2 h. To this reaction was added (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (103 mg, 0.208 mmol), KHCO3 (23 mg, 0.23 mmol), 2 M aq K2CO3 (400 μL), and Pd(PPh3)4 (24 mg, 21 μmol). The reaction was heated for another 1 h at 100° C. Finally, EtOH (absolute, 800 μL) and 10 M aq NaOH (500 μL) were added. The reaction was heated to 100° C. for another 1 h. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C33H36ClN5O3S: 618.2, 620.2 (M+H+); Found: 618.4, 620.2 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.43 (s, 1H), 8.05 (d, J=8.9 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J=9.1 Hz, 1H), 7.62-7.47 (m, 4H), 5.24 (s, 1H), 4.31-4.01 (m, 2H), 3.94 (s, 3H), 3.74-3.54 (m, 2H), 3.54-3.35 (m, 2H), 3.32-3.16 (m, 2H), 3.00 (s, 3H), 2.61 (s, 3H), 0.97 (s, 9H).

Provenance & Evidence