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

Participants

Reaction Steps

4-[6-[(3R)-3-Ethyl-4-morpholinyl]-2-(methylamino)-4-pyrimidinyl]-2,6-difluorobenzonitrile (690 mg, 1.92 mmol) was taken up in DMF (6 mL) followed by the addition of sodium ethoxide (1.1 M, 1.75 mL, 1.92 mmol). The reaction was then allowed to stir at room temperature. The reaction was diluted with EtOAc (20 mL) and washed with H2O (25 mL). The H2O was then back extracted with EtOAc (20 mL). The organics were dried and concentrated to afford a yellow oil that was then dissolved in CH3CN (5 mL) and transferred to a 20 mL microwave vial, followed by the addition of hydrazine (0.241 mL, 7.68 mmol) and Hunig's base (2.68 mL, 15.36 mmol). The reaction was irradiated at 140° C. for 2 hours. Another equivalent of hydrazine (0.120 mL, 3.84 mmol) was added to the reaction and it was irradiated at 140° C. for 30 minutes. The reaction was concentrated and purified via flash chromatography (0-50%, 80:20:2 CH2Cl2:CH3OH:NH4OH, 60 g). Fractions were combined and concentrated to afford the title compound (398.8 mg) as a yellow solid. LC-MS (ES) m/z=398 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.88 (t, J=7.5 Hz, 3H), 1.45 (t, J=7.0 Hz, 3H), 1.60-1.80 (m, 2H), 2.79-2.85 (m, 3H), 3.06-3.15 (m, 1H), 3.40-3.48 (m, 1H), 3.49-3.55 (m, 1H), 3.81-3.87 (m, 1H), 3.87-3.92 (m, 1H), 4.17-4.25 (m, 3H), 4.34 (bs, 1H), 4.99 (s, 2H), 6.50 (bs, 2H), 6.93 (bs, 1H), 7.52 (bs, 1H), 11.52 (bs, 1H).

Provenance & Evidence