Hydrazine hydrate (1:1) → HCID 66991086, compound

Participants

Reaction Steps

To a solution of 1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-(phenylmethyl)-6-(trifluoromethyl)-3-piperidinecarboxamide (66 mg, 0.129 mmol) in ethanol (2 mL) into a 5 mL microwave vial was added hydrazine monohydrate (0.121 mL, 3.86 mmol). The reaction was capped and heated overnight. Since the reaction was not completed, additional 50 uL of hydrazine monohydrate was added and heated overnight. The reaction was concentrated then re-dissolved in 1 mL of DMSO and purified on HPLC (HPLC condition: open-access Gilson using Unipoint software with a Varian Polaris 5u C18(2) 100A, 50×30.00 mm 5 micron. 10-minute run (35 mL/min, 25% CH3CN/H2O, 0.1% TFA to 50% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined and the volume was reduced under vacuum until most of the CH3CN was removed. Saturated aqueous NaHCO3 (10 mL) was added, and the resulting mixture was extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The resulting material was transferred into a vial and water was added and freeze dried overnight to afford the title compound (27 mg) as a light yellow solid. LC-MS (ES) m/z=525 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.81-1.88 (m, 3H), 2.06-2.14 (m, 1H), 2.43-2.49 (m, 1H), 2.84 (bs, 3H), 3.14 (bs, 1H), 4.20-4.43 (m, 2H), 5.40 (s, 2H), 6.80 (bs, 1H), 7.22-7.31 (m, 3H), 7.31-7.38 (m, 2H), 7.62-7.69 (m, 1H), 7.71-7.75 (m, 1H), 8.02 (bs, 1H), 8.54 (t, J=5.9 Hz, 1H), 11.53 (s, 1H).

Provenance & Evidence