Hydrazine hydrate (1:1) → 4-[3-[(2-aminoethyl)amino]-1H-indazol-5-yl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile

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Reaction Steps

A mixture of crude 5-(3,5-dicyano-2,6-dimethyl-1,4-dihydro-pyridin-4-yl)-3-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethylamino]-indazole-1-carboxylic acid tert-butyl ester (110 mg), hydrazine hydrate (80%, 0.039 mL, 0.62 mmol) and ethanol (1 mL), was heated at reflux for 2 hours. On cooling the reaction mixture was concentrated and the residue taken up in THF and aqueous HCl (4M) and heated at reflux for 1 hour. On cooling the reaction mixture was concentrated and the residue purified by preparative reverse phase HPLC to give 4-[3-[(2-aminoethyl)amino]-1H-indazol-5-yl]-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarbonitrile (38 mg) (Cpd. No. 308, Table 8). 1H-NMR (DMSO-D6, 300 MHz): δ=11.38 (br s, 1H), 9.46 (br s, 1H), 7.52 (s, 1H), 7.20 (d, 1H), 7.12 (dd, 1H), 5.93 (t, 1H), 4.34 (s, 1H), 3.21 (m, 2H), 2.75 (t, 2H), 2.01 (s, 6H) ppm.

Provenance & Evidence