Diethyl 2-[(3-methylisothiazol-5-ylamino)methylene]malonate → Ethyl 3-methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxylate

HRID 2404940Notes

Reaction equation

[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][CH:8]=[C:9]([C:15]([O:17]CC)=O)[C:10]([O:12][CH2:13][CH3:14])=[O:11])[S:4][N:3]=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[CH3:1][C:2]1[C:6]2[C:15](=[O:17])[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][NH:7][C:5]=2[S:4][N:3]=1

Participants

Conditions

Temperature: 259 °C

Procedure

Diethyl 2-((3-methylisothiazol-5-ylamino)methylene)malonate (10 g, 35.17 mmol) was added to refluxing diphenyl ether (40 mL) and the reaction was held at reflux (259° C.) for 3.5 h. After the starting material had been consumed, the reaction was allowed to cool to room temperature. The product was precipitated as a dark brown solid by adding diethyl ether (100 mL) to the cooled reaction mixture. The solid was filtered, washed with ether and allowed to air dry. The product ethyl 3-methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxylate was obtained as a brown powder (5.5 g, 66% yield). LC/MS m/z 239.0 [M+H]+, retention time 0.91 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min).

Workup

customAfter the starting material had been consumed
temperatureto cool to room temperature
customThe product was precipitated as a dark brown solid
additionby adding diethyl ether (100 mL)
customto the cooled reaction mixture
filtrationThe solid was filtered
washwashed with ether
customto air dry

Sources & evidence

ORD record: ord-7e962b383cb24a61a420e043479cfabc
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08802844B2

Reaction notes

Loading…