Hydrazine hydrate (1:1) → HCID 66990451, compound

Participants

Reaction Conditions

Reaction Steps

To cis-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclopentyl-6-(trifluoromethyl)-3-piperidinecarboxamide (37 mg, 0.075 mmol) in ethanol (2 mL) was added hydrazine monohydrate (0.11 mL, 2.26 mmol) into a 5 mL sealable vial, and the reaction was capped and heated overnight at 100° C. The reaction was concentrated, then redissolved 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 by reduce pressure until most of the CH3CN was removed. To the resulting aqueous mixture was added saturated aqueous NaHCO3 (10 mL) solution. The mixture was then extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The resulting material was transferred to a vial and water was added to freeze dried overnight and afford the title compound (20 mg) as a light yellow solid. LC-MS (ES) m/z=503 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.30-1.45 (m, 3H), 1.47-1.58 (m, 2H), 1.64 (dd, J=8.3, 4.3 Hz, 2H), 1.73-1.87 (m, 5H), 2.08 (bs, 1H), 2.33 (d, J=1.8 Hz, 1H), 2.84 (bs, 3H), 3.94-4.07 (m, 1H), 5.39 (s, 2H), 6.78 (bs, 2H), 7.62-7.74 (m, 2H), 7.94 (d, J=7.1 Hz, 1H), 8.02 (bs, 1H), 11.52 (s, 1H).

Provenance & Evidence