Dimethyl Sulfoxide → N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-4-(2-methylpyridin-4-yl)phenyl)acetamide

HRID 592191Notes

Reaction equation

[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][C:19]3[CH:24]=[CH:23][C:22](Cl)=[C:21]([F:26])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:28][C:29]1[CH:34]=[C:33]([Sn](CCCC)(CCCC)CCCC)[CH:32]=[CH:31][N:30]=1.CS(C)=O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:27])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:33]4[CH:32]=[CH:31][N:30]=[C:29]([CH3:28])[CH:34]=4)=[C:21]([F:26])[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

To the mixture of N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-chloro-3-fluorophenyl)acetamide 168-2 (80 mg, 0.2 mmol) and 2-methyl-4-(tributylstannyl)pyridine (78 mg, 0.2 mmol) in DMF (0.6 mL) was added [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (33 mg, 0.04 mmol). The reaction was stirred at 110° C. for 20 hours. After cooling down to room temperature, the reaction mixture was diluted into DMSO and purified by reverse-phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-fluoro-4-(2-methylpyridin-4-yl)phenyl)acetamide 168 as white solid. MS m/z 448.1 (M+1); 1H NMR 400 MHz (DMSO-d6) δ10.57 (s, 1H), 8.52 (d, 1H), 8.04 (s, 1H), 7.93 (d, 1H), 7.59 (m, 1H), 7.44-7.29 (m, 5H), 3.77 (s, 2H), 3.58 (b, 2H), 3.14 (b, 2H), 3.08 (b, 2H), 2.55 (s, 2H), 2.51 (s, 3H), 2.04 (s, 3H).

Workup

temperatureAfter cooling down to room temperature
custompurified by reverse-phase HPLC

Sources & evidence

ORD record: ord-65c03d2d00f440c8b739ceec4be40ae6
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238646B2

Reaction notes

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