Hydrazine hydrate (1:1) → 4-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-amine

Participants

Reaction Conditions

Reaction Steps

To 3-chloro-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-4-pyridinecarbonitrile (80 mg, 0.181 mmol) was added hydrazine monohydrate (0.266 mL, 5.43 mmol) to a 5 mL sealable vial with Ethanol (3 mL). The reaction was then capped and heated at 100° C. overnight. Observed 80% product and 20% SM. Additional hydrazine monohydrate (0.266 mL, 5.43 mmol) was added and heating was continued overnight. The reaction was concentrated then dissolved in 3 mL of DMSO and purified by HPLC: (HPLC condition: Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 ml/min, 17% ACN/H2O, 0.1% TFA to 42% ACN/H2O, 0.1% TFA) with UV detection at 220 nm). Product fractions were combined and the volume was reduced to remove most of the MeCN. To the water left behind was added saturated NaHCO3 and it was extracted with EtOAc (3×15 mL). The organics were combined and washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated. The residue was then transferred into a 40 mL vial with MeCN, water was added and the solution was freeze-dried to afford 4-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-1H-pyrazolo[3,4-c]pyridin-3-amine (20 mg, 25.3% yield) as a white solid. LC/MS (ES) m/z=438.4 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 12.29 (s, 1H), 8.74 (s, 1H), 8.18 (d, J=8.34 Hz, 1H), 7.93 (s, 1H), 7.69 (s, 1H), 7.56-7.67 (m, 3H), 7.44 (s, 1H), 7.33 (d, J=8.34 Hz, 1H), 4.61 (br. s., 2H), 4.30 (t, J=8.46 Hz, 2H), 4.05 (s, 2H), 3.26-3.30 (m, 2H).

Provenance & Evidence