Hydrazine hydrate (1:1) → HCID 86645974, compound

Participants

Reaction Steps

To a cooled (−78° C.) solution of the ester (1.16 g, 3 mmol) in dry CH2Cl2 (20 ml) under argon atmosphere DIBAH (1M in hexanes, 3.6 ml) was added dropwise over 15 min via syringe; once the addition was complete, the resulting solution was stirred at −78° C. for 1 h. The reaction was quenched pouring the cold solution into a saturated NH4Cl solution (10 m). 1M HCl (10 ml) was added and the biphasic mixture was stirred vigorously for 10 min. The layers were separated and the organic one was washed with brine while the aqueous was extracted with Et2O (2×10 ml). The collected organic extracts were dried over anhydrous Na2SO4 and concentrated to afford of (4R)-3-oxo-4-(4-{[4-(trifluoromethyl)-1,3-thiazol-2-yl]amino}phenyl)pentanal (728 mg) as a white waxy solid, used without further purification. To a solution of the aldehyde (728 mg) in EtOH/THF (2:1, 15 ml), hydrazine monohydrate (0.495 ml, 10.2 mmol) was added and the mixture refluxed for 30 min. After cooling at room temperature, the mixture was quenched with a saturated NH4Cl solution and extracted with EtOAc (3×25 ml). The collected organic extracts were washed with brine, dried over anhydrous Na2SO4 and evaporated under reduced pressure to give N-{4-[(1R)-1-(1H-pyrazol-5-yl)ethyl]phenyl}-4-(trifluoromethyl)-1,3-thiazol-2-amine (421 mg, 1.24 mmol) as a colourless oil (61%). 1H-NMR (CD3OD): δ 9.40 (bs, 1H, NH); 7.50 (d, 1H, J=2.5 Hz); 7.40 (d, 2H, J=7 Hz), 7.35 (d, 2H, J=7 Hz), 7.15 (s, 1H), 6.15 (d, 1H, J=2.5 Hz), 3.80 (q, 1H, J=7 Hz), 1.60 (d, 3H, J=7 Hz).

Provenance & Evidence