Hydroxylamine → Ethyl 1-[4-amino-6-(2-methoxy-5-methylphenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of the title compound from Example 19 Step D (1.2 g, 2.7 mmol), DMF (15 mL), water (1.5 mL) and tin (II) chloride dihydrate (1.8 g, 7.9 mmol) was heated at 70° C. for 1.5 h, leading to reduction of the nitro group to the corresponding hydroxylamine. A second addition of tin (II) chloride dehydrate (2.4 g, 10.6 mmol) followed by heating at 100° C. overnight led to little progress. Water was added, and the reaction mixture was extracted with hexanes-EtOAc. The organic phase was separated and passed through a pad of silica gel. Hydrogenation using Pd-black (450 mg, 4.2 mmol) in EtOAc:EtOH (100 mL, 1:1 v/v) under 50 psi H2, followed by filtration and concentration, provided the title compound: LCMS m/z 421.6 [M+H]+; 1H NMR (400 MHz, acetone-d6) δ 8.09 (s, 1H), 7.71 (d, J=2.1 Hz, 1H), 7.45 (d, J=1.9 Hz, 1H), 7.13 (dd, J=8.4 Hz, 2.1 Hz, 1H), 6.96 (d, J=8.4 Hz, 1H), 6.84 (d, J=1.9 Hz, 1H), 4.31 (q, J=7.1 Hz, 2H), 3.82 (s, 3H), 2.26 (s, 3H), 1.34 (t, J=7.1 Hz, 3H).

Provenance & Evidence