Ethyl 5-[2-(acetylamino)pyridin-4-yl]-4-cyano-3-iodothiophene-2-carboxylate → Ethyl 5-[2-(acetylamino)pyridin-4-yl]-3-(4-chlorobenzyl)-4-cyanothiophene-2-carboxylate

HRID 2401973Notes

Reaction equation

[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:15][C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:13](I)[C:12]=2[C:22]#[N:23])[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2].[Cl-].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][Zn+])=[CH:28][CH:27]=1>O1CCCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[C:1]([NH:4][C:5]1[CH:10]=[C:9]([C:11]2[S:15][C:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:13]([CH2:30][C:29]3[CH:32]=[CH:33][C:26]([Cl:25])=[CH:27][CH:28]=3)[C:12]=2[C:22]#[N:23])[CH:8]=[CH:7][N:6]=1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of ethyl 5-[2-(acetylamino)pyridin-4-yl]-4-cyano-3-iodothiophene-2-carboxylate (0.209 g, 0.474 mmol) in tetrahydrofuran (3.3 mL) was added 4-chlorobenzylzinc chloride (0.50M solution in tetrahydrofuran, 1.89 mL, 0.947 mmol) and bis(tri-t-butylphosphine)palladium(0) (0.0182 g, 0.0355 mmol) under argon. The solution was stirred at 60° C. for 3 hours. The reaction was allowed to cool to room temperature and then the solvent was evaporated in vacuo. Column chromatography was performed to yield the title compound (0.159 g, 76%). LCMS: (FA) ES+, 440. 1H NMR (400 MHz, CDCl3) δ: 8.66 (br s, 1H), 8.60 (br s, 1H), 8.38 (d, J=5.27 Hz, 1H), 7.51-7.47 (m, 1H), 7.33-7.23 (m, 4H), 4.51 (s, 2H), 4.39 (q, J=7.03 Hz, 2H), 2.24 (s, 3H), 1.39 (t, J=7.03 Hz, 3H).

Workup

temperatureto cool to room temperature
customthe solvent was evaporated in vacuo

Sources & evidence

ORD record: ord-78b39a5d387c4aee8c3343902abef025
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796271B2

Reaction notes

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