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

HRID 1958025Notes

Reaction equation

[NH2:1][C:2]1[N:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[S:5][C:6]=1[C:7]#[N:8].[C:15](Cl)(=[O:17])[CH3:16]>N1C=CC=CC=1>[C:7]([C:6]1[S:5][C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:3][C:2]=1[NH:1][C:15](=[O:17])[CH3:16])#[N:8]

Participants

Conditions

Temperature: 80 °C

Procedure

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)).

Workup

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

Sources & evidence

ORD record: ord-4d9358094ee74517b1de48ad53984aa7
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410095B2

Reaction notes

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