Water → 3-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)-2-hydroxypropyl methanesulfonate

HRID 595715Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[C:5]([CH2:18][CH:19]([OH:22])[CH2:20][OH:21])=[CH:4][CH:3]=1.[CH3:23][S:24](Cl)(=[O:26])=[O:25].O>C1COCC1>[CH3:23][S:24]([O:21][CH2:20][CH:19]([OH:22])[CH2:18][C:5]1[C:6]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=1)(=[O:26])=[O:25]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 3-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)propane-1,2-diol (100 mg, 0.31 mmol) and TEA (94 mg, 0.93 mmol) in THF (6 mL) was stirred under N2 at 0° C., MsCl (36 mg, 0.31 mmol) was added dropwise. The reaction was stirred at 0° C. for 1 h and RT overnight. Water was added and after extraction with EA, the organic layer was washed with water, brine, dried over Na2SO4 and concentrated on a rotary evaporator. The residue was purified by column chromatography (PE:EA=2:1˜1:1) to give the product of 3-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)-2-hydroxypropyl methanesulfonate (60 mg, yield: 48%). 1H-NMR (MeOD, 400 MHz) δ 7.80 (d, J=7.6 Hz, 1H), 7.26˜7.32 (m, 2H), 7.09˜7.11 (m, 1H), 7.04 (s, 1H), 6.70 (t, J=7.6 Hz, 1H), 4.20˜4.29 (m, 3H), 3.09˜3.13 (m, 5H). MS (M+H)+: 399/401.

Workup

stirringThe reaction was stirred at 0° C. for 1 h and RT overnight
extractionafter extraction with EA
washthe organic layer was washed with water, brine
dry with materialdried over Na2SO4
concentrationconcentrated on a rotary evaporator
customThe residue was purified by column chromatography (PE:EA=2:1˜1:1)

Sources & evidence

ORD record: ord-cfd1aed4c5234e6280abcac7c2b6d935
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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