Hydrazine → 6-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-4-fluoro-1H-indazol-3-amine

Participants

Reaction Steps

4-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile (0.453 g, 1.261 mmol) was taken up in CH3CN (5 mL) followed by the addition of hydrazine (0.158 mL, 5.04 mmol) and Hunig's base (1.76 mL, 10.1 mmol) in a 20 mL microwave vial. The reaction was irradiated at 150° C. for 1 hour. The reaction mixture was concentrated and purified by reverse phase HPLC (8-28% CH3CN/H2O, 0.1% TFA). Fractions were combined and diluted with EtOAc. The organics were washed with saturated NaHCO3 solution (2×) 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 (137 mg) as a white fluffy powder. LC-MS (ES) m/z=372 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.88 (t, 3H), 1.60-1.81 (m, 2H), 2.82 (d, J=4.0 Hz, 3H), 3.05-3.16 (m, 1H), 3.43 (d, J=2.53 Hz, 1H), 3.51 (dd, J=11.5, 2.9 Hz, 1H), 3.83 (d, J=11.4 Hz, 1H), 3.89 (dd, J=11.1, 3.0 Hz, 1H), 4.03 (d, J=7.1 Hz, 1H), 4.16-4.28 (m, 1H), 4.30-4.43 (m, 1H), 5.26 (s, 2H), 6.58 (bs, 2H), 7.36 (d, J=12.4 Hz, 1H), 7.84 (bs, 1H), 11.89 (s, 1H).

Provenance & Evidence