Hydrazine hydrate (1:1) → HCID 178511278, compound

Participants

Reaction Conditions

Reaction Steps

Hydrazine monohydrate (0.28 mL, 2.7 eq) was added to a solution of trans-2-[4-(4-benzotriazol-1-yl-pyrimidin-2-ylamino)-cyclohexylmethyl]-isoindole-1,3-dione (976 mg, 1 equivalent) in EtOH (60 mL). The reaction mixture was stirred overnight at 70° C., a second aliquot of hydrazine monohydrate (0.22 mL, 2.0 eq) was then added and the mixture was stirred at reflux for 7 hours. The solvent was then evaporated under reduced pressure, the residue was dissolved in a mixture of isopropanol and chloroform and it was acidified until pH 3 by the addition of HCl (1 M). The organic phase was washed 3 times with water. The aqueous phase was basified to pH 8-9 by the addition of NaOH (1 M) and it was extracted 5 times with a mixture of isopropanol and chloroform. The combined organic extracts were dried over Na2SO4, filtered and the solvent was evaporated under reduced pressure. This acid/base extraction procedure was repeated 3 times in order to remove phthalazinone. trans-(4-Aminomethyl-cyclohexyl)-(4-benzotriazol-1-yl-pyrimidin-2-yl)-amine was obtained in 71% purity (450 mg, 65% yield). 1H NMR (400 MHz, CD3OD) δ ppm 8.53-8.85 (1 H, bd), 8.40 (1 H, d, J=5.50 Hz), 8.09 (1 H, d, J=8.31 Hz), 7.67 (1 H, m), 7.53 (1 H, m), 7.39 (1 H, d, J=5.50 Hz), 3.76-3.89 (1 H, m), 2.60 (2 H, d, J=6.60 Hz), 2.11-2.28 (2 H, m), 1.88-2.02 (2 H, m), 1.08-1.54 (5 H, m).

Provenance & Evidence