2,6-Lutidine → HCID 67188835, compound

Participants

Reaction Conditions

Reaction Steps

(R)-3-((R)-3-Oxo-cyclopentyl)-2-(3-trifluoromethyl-phenyl)-propionic acid (85 mg, 0.28 mmol) was dissolved in methylene chloride (2 mL) and N,N-dimethylfomamide (three drops) at 25° C. under argon. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 150 μL, 0.29 mmol) which produced gas evolution and it was then stirred at 25° C. for 30 minutes after which time it was concentrated in vacuo. The residue was then dissolved in methylene chloride (2 mL) and added dropwise into a solution of 1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-ylamine (prepared in Example 67, 68 mg, 0.28 mmol), 2,6-lutidine (66 μL, 0.56 mmol) and methylene chloride (2 mL) at 0° C. It was then allowed to warm to 25° C. and stirred for 1.5 h. After this time, the reaction was quenched with a small amount of methanol and then concentrated with silica gel (2 g) in vacuo and purified on Biotage Flash chromatography system (40S column, silica gel, 50% ethyl acetate/hexanes) to afford (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-3-((R)-3-oxo-cyclopentyl)-2-(3-trifluoromethyl-phenyl)-propionamide (85 mg, 57%) as a yellow oil: [α]25589=−9.4° (c=0.16, methanol); ES-HRMS m/e calcd for C26H36N3O3SiF3 (M+Na)+ 546.2370, observed 546.2367; 1H NMR (300 MHz, CDCl3) δ-0.06 (s, 6H, 2×SiCH3), 0.83 (s, 9H, 3×CH3), 1.57 (m, 1H, CH), 1.82-2.47 (m, 8H, 4×CH2), 3.57 (m, 1H, ArCHCO), 3.85 (t, J=5.3 Hz, 2H, OCH2), 4.05 (t, J=5.3 Hz, 2H, NCH2), 6.64 (d, J=2.2 Hz, 1H, Ar), 7.32 (d, J=2.2 Hz, 1H, Ar), 7.46-7.62 (m, 4H, Ar), 7.67 (brs, 1H, NH).

Provenance & Evidence