Hydrazine hydrate (1:1) → HCID 46216155, compound

Participants

Reaction Conditions

Reaction Steps

(2S,5R)-4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-5-methyl-N-phenyl-2-morpholinecarboxamide (57 mg, 0.132 mmol) was dissolved in ethanol (3 mL) with stirring in a 5 mL microwave vessel. Hydrazine monohydrate (150 μL, 3.09 mmol) was added, and the mixture was capped and heated at 100° C. in an oil bath for 24 hours. The mixture was partitioned between EtOAc and water, and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried (MgSO4) filtered and evaporated. Purification by silica gel chromatograpy (Analogix RS-4 g) eluting with 90:10:1 CHCl3:CH3OH:conc. aq. NH4OH afforded the title compound (19 mg, 0.041 mmol, 30.8% yield) as a colorless film/foam. NMR showed a residual solvent peak with singlets at 1.9 and 3.36, so the material was azeotroped with CH3CN and then triturated to give a white powder. 1H NMR (400 MHz, DMSO-d6): δ 1.24 (d, J=6.3 Hz, 3H), 3.04 (bs, 1H), 3.82 (d, J=9.8 Hz, 1H), 3.93 (d, J=11.1 Hz, 1H), 4.07-4.23 (m, 1H), 4.53 (bs, 2H), 5.39 (bs, 2H), 6.22 (bs, 2H), 6.61 (s, 1H), 7.10 (t, J=7.1 Hz, 1H), 7.34 (t, J=7.7 Hz, 2H), 7.60 (d, J=8.3 Hz, 1H), 7.69-7.78 (m, 3H), 7.96 (s, 1H), 9.87 (bs, 1H), 11.52 (s, 1H).

Provenance & Evidence