Triethylamine → Adamantane-1-carboxylic acid{4,5-dimethyl-3-[2-(2,2,2-trifluoro-ethoxy)-ethyl]-3H-thiazol-2-ylidene}-amide

To a solution of Example 85A (0.20 g, 0.8 mmol) in THF (10 mL) was added triethylamine (0.4 mL) and adamantane-1-carbonyl chloride (0.2 g, 1 mmol). The mixture was heated at reflux overnight and then concentrated under reduced pressure. The residue was diluted with ethyl acetate, washed with 1M aqueous NaHCO3, dried (Na2SO4), filtered, and concentrated. Purification by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes afforded 10 mg of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.60-1.75 (m, J=28.8 Hz, 6H), 1.83 (d, J=2.7 Hz, 6H), 1.93-2.01 (m, 3H), 2.15 (s, 3H), 2.20 (s, 3H), 3.92 (t, J=5.3 Hz, 2H), 4.09 (q, J=9.5 Hz, 2H), 4.28 (t, J=5.3 Hz, 2H); MS (ESI+) m/z 417 (M+H)+; Anal. Calculated for C20H17F3N2O2S: C, 57.67; H, 6.53; N, 6.73. Found: C, 57.53; H, 6.55; N, 6.69.

1. temperatureThe mixture was heated
2. temperatureat reflux overnight
3. concentrationconcentrated under reduced pressure
4. additionThe residue was diluted with ethyl acetate
5. washwashed with 1M aqueous NaHCO3
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customPurification by preparative HPLC on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size)

ORD record

ord-79d1f983d1574cb6ad4d6417de51fc14

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006275B2