Trifluoromethanesulfonic anhydride → 6-chloro-4-(4-fluoro-1H-indol-2-yl)pyridin-3-yl trifluoromethanesulfonate

HRID 595673Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[C:15]([F:18])[CH:14]=[CH:13][CH:12]=3)[CH:3]=1.CCN(C(C)C)C(C)C.[O:28](S(C(F)(F)F)(=O)=O)[S:29]([C:32]([F:35])([F:34])[F:33])(=O)=[O:30]>CN(C1C=CN=CC=1)C.C(Cl)Cl.O>[F:33][C:32]([F:35])([F:34])[S:29]([O:8][C:5]1[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][C:4]=1[C:9]1[NH:10][C:11]2[C:16]([CH:17]=1)=[C:15]([F:18])[CH:14]=[CH:13][CH:12]=2)(=[O:30])=[O:28]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of 6-chloro-4-(4-fluoro-1H-indol-2-yl)pyridin-3-ol (prepared using similar method described in Example 1, 500 mg, 1.9 mmol), DIPEA (490 mg, 3.8 mmol) and DMAP (5 mg, 0.02 mmol) in DCM (2 mL) was added Tf2O (1.07 g, 3.8 mmol) dropwise at 0° C. under nitrogen. The mixture was stirred at 25° C. for 5 hours. The mixture was diluted with H2O extracted with EtOAc, then the combined organic phase was washed with brine, dried over Na2SO4 and concentrated in vacuo to give the crude product. It was purified by column (PE:EA=5:1) to obtain the product of 6-chloro-4-(4-fluoro-1H-indol-2-yl)pyridin-3-yl trifluoromethanesulfonate (600 mg, yield: 80%). 1H-NMR (CDCl3, 400 MHz) δ 8.71 (s, 1H), 8.39 (s, 1H), 7.64 (s, 1H), 7.18˜7.20 (m, 3H), 6.77˜6.82 (m, 1H). MS (M+H)+: 395/397.

Workup

extractionextracted with EtOAc
washthe combined organic phase was washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customto give the crude product
customIt was purified by column (PE:EA=5:1)

Sources & evidence

ORD record: ord-0dfc593eb76d4ea298d2fe1795376fb7
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

Loading…