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

Participants

Reaction Steps

4-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2-fluorobenzonitrile (0.464 g, 1.359 mmol) was taken up in CH3CN (5 mL) followed by the addition of hydrazine (0.171 mL, 5.44 mmol) and Hunig's (1.899 mL, 10.87 mmol) in a 20 mL microwave vial. The reaction was irradiated at 150° C. for 1 hour. The reaction mixture was then concentrated and the resulting residue was purified using reverse phase HPLC (5-30% 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 (×1). 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=354 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.89 (t, 3H), 1.60-1.82 (m, 2H), 2.83 (d, J=4.0 Hz, 3H), 3.10 (d, J=2.3 Hz, 1H), 3.43 (d, J=2.5 Hz, 1H), 3.52 (dd, J=11.5, 2.9 Hz, 1H), 3.84 (d, J=11.4 Hz, 1H), 3.89 (dd, J=11.2, 3.2 Hz, 1H), 4.03 (q, J=7.1 Hz, 1H), 4.14-4.26 (m, 1H), 4.29-4.38 (m, 1H), 5.38 (s, 2H), 6.55 (bs, 2H), 7.59 (d, J=8.6 Hz, 1H), 7.71 (d, J=8.6 Hz, 1H), 7.97 (bs, 1H), 11.50 (bs, 1H).

Provenance & Evidence