Tributylvinyltin → 2-(2-chloro-5-vinylpyrimidin-4-yl)-4-fluoro-1H-indole

HRID 595722Notes

Reaction equation

FC(F)(F)S(O[C:7]1[C:8]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[C:20]([F:23])[CH:19]=[CH:18][CH:17]=3)=[N:9][C:10]([Cl:13])=[N:11][CH:12]=1)(=O)=O.[CH2:26]([Sn](CCCC)(CCCC)C=C)[CH2:27]CC.[Li+].[Cl-]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:13][C:10]1[N:9]=[C:8]([C:14]2[NH:15][C:16]3[C:21]([CH:22]=2)=[C:20]([F:23])[CH:19]=[CH:18][CH:17]=3)[C:7]([CH:26]=[CH2:27])=[CH:12][N:11]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a mixture of 2-chloro-4-(4-fluoro-1H-indol-2-yl)pyrimidin-5-yl trifluoromethanesulfonate (500 mg, 1.26 mmol), tributyl(vinyl)stannane (400 mg, 1.26 mmol) and anhydrous LiCl (150 mg, 3.54 mmol) in DMF (5 mL), Pd(PPh3)2Cl2 (50 mg, 0.07 mmol) was added under N2 protection. The reaction mixture was stirred at 60° C. for 1 h. Then it was concentrated in vacuo, and the residue was purified by column chromatography (PE:EA=10:1) to give the product of 2-(2-chloro-5-vinylpyrimidin-4-yl)-4-fluoro-1H-indole (250 g, yield: 72.3%). 1H-NMR (DMSO-d6, 400 MHz) δ 12.21 (br s, 1H), 8.85 (s, 1H), 7.41 (d, J=7.6 Hz, 1H), 7.21˜7.27 (m, 1H), 7.08˜7.20 (m, 2H), 6.87 (dd, J=10.4, 7.6 Hz, 1H), 6.01 (dd, J=17.6, 1.2 Hz, 1H), 5.72 (dd, J=11.2, 1.2 Hz, 1H). MS (M+H)+: 274/276.

Workup

additionwas added under N2 protection
concentrationThen it was concentrated in vacuo
customthe residue was purified by column chromatography (PE:EA=10:1)

Sources & evidence

ORD record: ord-9f02695eb16946ae9d23e098efa43336
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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