Diisopropylethylamine → 1,2,3,4-Tetrahydro-naphthalene-1-carboxylic acid (2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)amide

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Reaction Steps

To a solution of 1-[4-(4-amino-thiazol-2-yl)-piperidin-1-yl]-2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-ethanone (120 mg, 0.32 mmol) and diisopropylethylamine (0.2 mL, 0.96 mmol) in dichloromethane (5 mL) is added dropwise a solution of 1,2,3,4-tetrahydro-naphthalene-1-carbonyl chloride (74 mg, 0.38 mmol) in dichloromethane (3 mL) at 0° C. After stirring overnight at RT, the solvent is evaporated and the residue is purified by flash chromatography on silica gel (ethylacetate/cyclohexane 1:1) to give 1,2,3,4-tetrahydro-naphthalene-1-carboxylic acid (2-{1-[2-(5-methyl-3-trifluoromethyl-pyrazol-1-yl)-acetyl]-piperidin-4-yl}-thiazol-4-yl)amide (Compound No. 1.g.011, 82 mg, 48%). M.p.=179.2-181.3° C. 1H-NMR (400 MHz, CDCl3): δ=1.60-1.75 (m, 3H), 1.81-1.89 (m, 2H), 2.05-2.15 (m, 2H), 2.31 (s, 3H), 2.32-2.40 (m, 1H), 2.77-2.94 (m, 3H), 3.05-3.18 (m, 1H), 3.19-3.29 (m, 1H), 3.87 (t, 1H), 3.95-4.04 (m, 1H), 4.50-4.59 (m, 1H), 4.90-5.06 (2d, 2H, diastereotopic protons), 6.32 (s, 1H), 7.25-7.30 (m, 4H), 7.49 (s, 1H), 7.79 (br, 1H). MS: m/z=532 (M+1).

Provenance & Evidence