Methylamine → 6-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-N4-methyl-1H-indazole-3,4-diamine

Participants

Reaction Steps

To a 4 mL vial was added 4-[6-[(3R)-3-ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2,6-difluorobenzonitrile (100 mg, 0.278 mmol), DMF (1 mL), and methylamine in THF (2 M, 0.14 mL, 0.28 mmol). The reaction was stirred at room temperature for 2 hours. The reaction was then poured into EtOAc (10 mL) and the aqueous was extracted with EtOAc (2×). The organics were then dried over Na2SO4 and concentrated to afford a yellow oil that was taken up in CH3CN (1.5 mL) and added to a 5 mL microwave vial followed by the addition of hydrazine (0.035 mL, 1.113 mmol) and Hunig's base (0.39 mL, 2.23 mmol). The reaction was irradiated at 150° C. for 90 minutes. The reaction mixture was then concentrated and purified via reverse phase HPLC (10-30% CH3CN/H2O, 0.1% TFA). Fractions were combined and diluted with EtOAc. The organics were washed with saturated NaHCO3 solution that was back extracted with EtOAc. The organics were combined and dried over Na2SO4. The product was taken up in 2 mL H2O and lyophilized to afford the title compound (7 mg). LC-MS (ES) m/z=383 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.85-0.91 (m, 3H), 1.58-1.82 (m, 2H), 2.79-2.84 (m, 3H), 3.05-3.14 (m, 1H), 3.22-3.28 (m, 3H), 3.39-3.48 (m, 1H), 3.49-3.55 (m, 1H), 3.81-3.86 (m, 1H), 3.87-3.92 (m, 1H), 4.12-4.20 (m, 1H), 4.31 (bs, 1H), 4.85 (s, 2H), 6.43 (bs, 1H), 6.51 (bs, 1H), 6.96 (bs, 1H), 7.48 (bs, 1H), 11.58 (bs, 1H).

Provenance & Evidence