2-Aminothiazole → (3r,5r,7r)-N-(thiazol-2-yl)adamantane-1-carboxamide

HRID 255045Notes

Reaction equation

[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[C:7]12([C:17](Cl)=[O:18])[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][CH:9]([CH2:10]3)[CH2:8]1)[CH2:14]2.C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[NH:1][C:17]([C:7]12[CH2:16][CH:11]3[CH2:10][CH:9]([CH2:15][CH:13]([CH2:12]3)[CH2:14]1)[CH2:8]2)=[O:18]

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 2-aminothiazole (6.1 g, 61 mmol) in 250 mL. of THF at 0° C. was added a solution of adamantane-1-carbonyl chloride (11 g, 55 mmol) in 25 mL of THF, followed by triethylamine (17 ml, 0.12 mol). The mixture was warmed to 65° C., stirred for 4 hours, and then allowed to cool to ambient temperature. The mixture was diluted with ethyl acetate and washed twice with water and brine. The aqueous washings were combined and extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 20-40% ethyl acetate/hexanes gradient) afforded 11 g (78%) of the title compound, 1H NMR (CDCl3, 300 MHz) δ ppm 1.68-1.85 (m, 6 H), 1.97 (d, J=3.1 Hz, 6 H), 2.12 (s, 3 H), 6.96 (d, J=3.7 Hz, 1 H), 7.44 (d, J=3.4 Hz, 1 H), 8.92 (s, 1H); MS (DCI/NH3) m/z 263 (M+H)+.

Workup

temperatureto cool to ambient temperature
washwashed twice with water and brine
extractionextracted with ethyl acetate
dry with materialThe combined organic extracts were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification by column chromatography (SiO2, 20-40% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record: ord-4038502b0ce2440cb7875573781c5828
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875639B2

Reaction notes

Loading…