Water → (2-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)methanol

HRID 595716Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 3-(6-chloro-2-(4-fluoro-1H-indol-2-yl)pyridin-3-yl)-2-hydroxypropyl methanesulfonate (100 mg, 0.25 mmol) in DMF (5 mL) was stirred under N2 at 0° C. After NaH (30 mg, 60% in mineral oil, 0.75 mmol) was added, the mixture was stirred at 0° C. for 0.5 h and RT for 2 h. After cooling to 0° C., water was added and the mixture extracted with EtOAc. Then 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 (2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)methanol (70 mg, yield: 92%). 1H-NMR (CDCl3, 400 MHz) δ 7.50 (d, J=7.6 Hz, 1H), 7.37 (s, 1H), 7.13˜7.19 (m, 3H), 6.78 (t, J=7.6 Hz, 1H), 4.79˜4.84 (m, 1H), 3.69˜3.73 (m, 1H), 3.60˜3.62 (m, 1H), 3.38˜3.42 (m, 1H), 3.24 (d, J=16.4 Hz, 1H). MS (M+H)+: 303/305.

Workup

temperatureAfter cooling to 0° C.
extractionthe mixture extracted with EtOAc
washThen the 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-0265d2e67ffb4747b62703182fec0d4f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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