5-Amino-2-chloropyridine → Ethyl 3-(6-chloropyridin-3-ylamino)-2-(methylsulfonyl)acrylate

HRID 526159Notes

Reaction equation

C(O[CH:4]=[C:5]([S:11]([CH3:14])(=[O:13])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][N:17]=1>ClC1C=CC=CC=1>[Cl:15][C:16]1[N:17]=[CH:18][C:19]([NH:22][CH:4]=[C:5]([S:11]([CH3:14])(=[O:12])=[O:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:20][CH:21]=1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of ethyl 3-ethoxy-2-(methylsulfonyl)acrylate (7.0 g, 32 mmol) and 2-chloro-5-aminopyridine (4.1 g, 32 mmol) in chlorobenzene (16 mL) was stirred with heat at 135° C. for 3 h in a round bottomed flask that was equipped with a short path distillation apparatus to collect the ethanol generated during the reaction. The reaction was cooled, concentrated and the residue was purified by chromatography (silica, methylene chloride/ethyl acetate) to afford the desired product (8.2 g, 84%) as a pale yellow oil: 1H NMR (500 MHz, CDCl3) δ 10.61 (d, 13.4 Hz, 1H), 8.34 (d, J=13.4 Hz, 1H), 8.27 (d, J=2.9 Hz, 1H), 7.50 (dd, J=8.6, 3.0 Hz, 1H), 7.37 (d, J=8.6 Hz, 1H), 4.41 (q, J=7.2 Hz, 2H), 3.18 (s, 3H), 1.42 (t, J=7.2 Hz, 3H); ESI MS m/z 305 [M+H]+.

Workup

customwas equipped with a short path distillation apparatus
customto collect the ethanol
customgenerated during the reaction
temperatureThe reaction was cooled
concentrationconcentrated
customthe residue was purified by chromatography (silica, methylene chloride/ethyl acetate)

Sources & evidence

ORD record: ord-c6619382b57942519b5b78a35fe7ec34
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09345709B2

Reaction notes

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