Sodium Nitrite → HCID 58286959, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 8-fluoro-3-methyl-1-oxo-2-pyridin-3-yl-1,2-dihydro-isoquinoline-4-carboxylic acid [(S)-cyclopropyl-(3-fluoro-phenyl)-methyl]-amide (2a, 70.0 mg, 0.157 mmol), sodium nitrite (NaNO2, 77.0 mg, 1.12 mmol) in N,N-dimethylformamide (0.7 mL) was heated under microwave irradiation at 220° C. for 30 min. The obtained dark solution was quenched with 3M aq. HCl (5 ml), stirred for 20 min and partitioned with ethyl acetate (3×5 mL). Each organic solution was washed with 1M HCl (3×2 mL). The combined aq. solution was basified with NaHCO3 (pH=7) and extracted with ethyl acetate. The combined organic extracts were absorbed on 1 g SiO2 and flash chromatographed on 20 g silica gel with gradient heptane-ethyl acetate. The product came out with 75% ethyl acetate and only pure fractions were evaporated to give 7.1 mg of a brown residue, yield 10%. LC-MS (m/z) 444.6 (MH+); tR=1.26. 1H NMR (500 MHz, 70° C., DMSO-d6): 0.48 & 0.59 (two br. s, 2×2H, two CH2 of Cp), 1.27 (br. s, 1H, CH of Cp), 1.91 (br. s, 3H, Me), 4.51 (t, J=8.5 Hz, 1H, CHNH), 6.87 (overlapping d, J=8.1 Hz, 1H), 6.9 (overlapping br. s, 1H), 7.06 (br. T, J=8.3 Hz, 1H), 7.26 (d, J=10.5 Hz, 1H), 7.3 (d, J=7.6 Hz, 1H), 7.40 (q, J=7.2 Hz, 1H), 7.59-7.66 (br. m, 2H), 7.86 (br. m, 1H), 8.58 (s, 1H), 8.72 (s, 1H), 8.93 (br. d, J=7.8 Hz, NHCO), 12.46 (s, 1H, OH).

Provenance & Evidence