Acetyl chloride → N-[5-cyano-2-(4-morpholinyl)-1,3-thiazol-4-yl]acetamide

Temperatur

80 °C

To a 5 L round bottom flask equipped with a mechanical stirrer was added 4-amino-2-(4-morpholinyl)-1,3-thiazole-5-carbonitrile (200 g, 951 mmol) and N,N-dimethylaminopyridine (23.24 g, 190 mmol). The solids were taken up in Pyridine (2000 mL) and to this reaction solution was added acetyl chloride (74.7 g, 951 mmol) via an addition funnel. The reaction was heated to 80° C. and monitored by LCMS for conversion to product. Upon complete conversion (˜2 hours), the reaction was cooled to room temperature and the reaction was concentrated to a slurry, then subsequently diluted with a mixture of 0.1N NaOH (2 L) solution and methanol (140 mL). The mixture was rapidly stirred using a mechanical stirrer for 15 min, then the resulting precipitate was collected by filtration to provide the desired N-[5-cyano-2-(4-morpholinyl)-1,3-thiazol-4-yl]acetamide (218.2 g, 778 mmol, 82% yield) as a brown solid (1H NMR (400 MHz, DMSO-d6) δ ppm 2.04 (s, 3H) 3.40-3.53 (m, 4H) 3.62-3.77 (m, 4H) 10.88 (s, 1H)).

1. customTo a 5 L round bottom flask equipped with a mechanical stirrer
2. temperatureUpon complete conversion (˜2 hours), the reaction was cooled to room temperature
3. concentrationthe reaction was concentrated to a slurry
4. additionsubsequently diluted with a mixture of 0.1N NaOH (2 L) solution and methanol (140 mL)
5. customfor 15 min
6. filtrationthe resulting precipitate was collected by filtration

ORD-Eintrag

ord-4d9358094ee74517b1de48ad53984aa7

Quelldatensatz

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08410095B2