Reaktion #58432

Reaktionsgleichung

2-bromo-1-(3-fluorophenyl)ethanone

4-isothiocyanatopiperidine-1-carboxylic acid tert-butyl ester

cyanamide

potassium tert-butoxide

→

4-[4-amino-5-(3-fluorobenzoyl)thiazol-2-ylamino]piperidine-1-carboxylic acid tert-butyl ester

Ausbeute 62.0%

Lösungsmittel

tert-butanol

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeSolvent was removed
2. 2
   Sonstigethe solid residue purified by silica gel chromatography (60%-70% ethyl acetate/hexane)

Vorschrift

At 20° C., a mixture of 4-isothiocyanatopiperidine-1-carboxylic acid tert-butyl ester (2.4 g, 10 mmol) (Example 1) and cyanamide (0.42 g, 10 mmol) (Aldrich) in tert-butanol (5 mL) and acetonitrile (35 mL) was treated with potassium tert-butoxide (1.0 M/THF, 10 mL, 10 mmol, Aldrich) for 15 min. 2-bromo-1-(3-fluorophenyl)ethanone (2.0 g, 9.2 mmol)(Example 2) was added and the suspension was stirred for 2 h. Solvent was removed and the solid residue purified by silica gel chromatography (60%-70% ethyl acetate/hexane) to give 2.4 g (57% yield) of 4-[4-amino-5-(3-fluorobenzoyl)thiazol-2-ylamino]piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (DMSOd6, 300 MHz) δ1.36 (m, 2H, NCH2), 1.41 (s, 9H, 3CH3), 1.88 (m, 2H, NCH2), 2.88 (brd, 2H, NCH2), 3.6-4.0 (m, 1H, CH), 3.87 (m, 2H, NCH2), 7.31 (t, 1H, Aromatic), 7.38 (d, 1H, Aromatic), 7.48 (t, 1H, Aromatic), 7.51 (q, 1H, Aromatic), 8.01 (brd, 1H, NH), 8.48 (brd, 1H, NH), 8.48 (brd, 1H, NH), 8.70 (brd, 1H, NH).

Quelle