2,6-Lutidine → HCID 67189552, compound

Participants

Reaction Conditions

Reaction Steps

(R)-2-(4-methanesulfonyl-3-methyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionic acid (85 mg, 0.26 mmol) was dissolved in methylene chloride (2 mL) and N,N-dimethylformamide (three drops) at 25° C. under argon. To this solution was added dropwise a solution of oxalyl chloride in methylene chloride (2 M solution, 140 μL, 0.27 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, 63 mg, 0.26 mmol), 2,6-lutidine (62 μL, 0.52 mmol) and methylene chloride (2 mL) at 0° C. It was then allowed to warm to 25° C. and stirred for 1 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 80% ethyl acetate/hexanes) to afford (R)—N-{1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-2-(4-methanesulfonyl-3-methyl-phenyl)-3-((R)-3-oxo-cyclopentyl)-propionamide (109 mg, 77%) as a yellow oil: [α]25589=−50.0° (c=0.21, methanol); ES-HRMS m/e calcd for C27H41N3O5SSi (M+H)+ 548.2609, observed 548.2609; 1H NMR (300 MHz, CDCl3) δ −0.06 (s, 6H, 2×SiCH3), 0.84 (s, 9H, 3×CH3), 1.57 (m, 1H, CH), 1.82-2.47 (m, 8H, 4×CH2), 2.72 (s, 3H, ArCH3), 3.09 (s, 3H, SO2CH3), 3.55 (t, J=7.3 Hz, 1H, ArCHCO), 3.85 (t, J=5.3 Hz, 2H, OCH2), 4.06 (t, J=5.3 Hz, 2H, NCH2), 6.64 (d, J=2.2 Hz, 1H, Ar), 7.35 (m, 3H, Ar), 7.75 (brs, 1H, NH), 8.03 (d, Jo=8.2 Hz, 1H, Ar).

Provenance & Evidence