Hydrazine → HCID 58504683, compound

Participants

Reaction Steps

To a 20 mL vial was added 4-{2-amino-6-[(3R)-3-ethyl-4-morpholinyl]-4-pyrimidinyl}-2,6-difluorobenzonitrile (850 mg, 2.461 mmol), N,N-dimethylformamide (DMF) (5 mL) and sodium ethoxide 1M (2.461 mL, 2.461 mmol). The reaction was stirred for 30 min at room temperature. The reaction was then poured into EtOAc (10 mL) followed by H2O (15 mL). The aqueous was extracted with EtOAc (×1) and then dried over Na2SO4 and concentrated to a yellow solid that was taken up in acetonitrile (5 mL) and added to a 20 mL microwave vial followed by hydrazine (0.309 mL, 9.85 mmol) and DIEA (3.44 mL, 19.69 mmol). The reaction was sealed and heated in a microwave reactor at 150° C. for 3 h. The reaction mixture was concentrated to a yellow oil and purified via flash chromatography (120 g, 50-100%, DCM:MeOH:NH4OH). Fractions were combined and concentrated to afford 6-{2-amino-6-[(3R)-3-ethyl-4-morpholinyl]-4-pyrimidinyl}-4-(ethyloxy)-1H-indazol-3-amine (514 mg) as a tan solid. LC-MS (ES) m/z=384 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 0.87 (t, J=7.45 Hz, 3H), 1.45 (t, J=6.95 Hz, 3H), 1.58-1.80 (m, 2H), 3.01-3.14 (m, 1H), 3.37-3.47 (m, 1H), 3.46-3.56 (m, 1H), 3.83 (d, J=11.4 Hz, 2H), 3.85-3.91 (m, 1H), 4.21 (q, J=6.99 Hz, 3H), 4.25-4.39 (m, 1H), 5.00 (s, 2H), 6.07 (s, 2H), 6.49 (s, 1H), 6.90 (s, 1H), 7.47 (s, 1H), 11.53 (s, 1H).

Provenance & Evidence