2-Chloroethyl isocyanate → Ethyl 5-(3-(2-chloroethyl)ureido)-3-methylthiophene-2-carboxylate

HRID 560543Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([NH2:14])=[C:9](CC)[C:10]=1[CH3:11])=[O:5])[CH3:2].[Cl:15][CH2:16][CH2:17][N:18]=[C:19]=[O:20]>C(#N)C>[Cl:15][CH2:16][CH2:17][NH:18][C:19](=[O:20])[NH:14][C:8]1[S:7][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[C:10]([CH3:11])[CH:9]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of ethyl 5-amino-3-methylthiophene-2-carboxylic acid ethyl ester (4.75 g, 25.6 mmol) and 2-chloroethyl-isocyanate (2.63 ml, 30.8 mmol) in anhydrous acetonitrile (50 mL) was stirred under nitrogen atmosphere at 70° C. for 20 h, then was cooled to ambient temperature and concentrated in vacuo. The residue was triturated with hexanes/ethyl acetate to afford an off-white solid. The filtrate was concentrated in vacuo, and the residue was triturated with hexanes/ethyl acetate to afford an off white solid. The combined solid was dried to afford the title compound in 82% yield (6.11 g): 1H NMR (300 MHz, CDCl3) δ 7.73 (br s, 1H), 6.31 (s, 1H), 5.60 (t, J=5.0 Hz, 1H), 4.27 (q, J=7.1 Hz, 2H), 3.69-3.59 (m, 4H), 2.44 (s, 3H), 1.33 (t, J=7.1 Hz, 3H); MS (ES+) m/z 291.2 (M+1).

Workup

temperaturewas cooled to ambient temperature
concentrationconcentrated in vacuo
customThe residue was triturated with hexanes/ethyl acetate
customto afford an off-white solid
concentrationThe filtrate was concentrated in vacuo
customthe residue was triturated with hexanes/ethyl acetate
customto afford an off white solid
customThe combined solid was dried

Sources & evidence

ORD record: ord-dc9c216a662a4b6fbe1baad44742ef74
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063084B2

Reaction notes

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