Potassium Cyanide → 2-(2-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)acetonitrile

HRID 595733Notes

Reaction equation

CS(O[CH2:6][CH:7]1[N:16]2[C:17]3[CH:18]=[CH:19][CH:20]=[C:21]([F:24])[C:22]=3[CH:23]=[C:15]2[C:14]2[N:13]=[C:12]([Cl:25])[CH:11]=[CH:10][C:9]=2[CH2:8]1)(=O)=O.[C-:26]#[N:27].[K+]>CN(C=O)C.O>[Cl:25][C:12]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:6][C:26]#[N:27])[N:16]3[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([F:24])[C:22]=4[CH:23]=[C:15]3[C:14]=2[N:13]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)methyl methanesulfonate (1 g, 2.52 mmol) and KCN (491 mg, 7.55 mmol) in DMF (15 mL) was stirred at 80° C. for 15 hours. The mixture was diluted with water (30 mL) and extracted with EA (20 mL×3). The organic layer was washed with brine (30 mL), dried over Na2SO4 and concentrated. The residue was purified by column (PE:EA=1:1) to afford the desired product of 2-(2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)acetonitrile (600 mg, yield: 73%). 1H-NMR (CDCl3, 400 MHz) δ 7.49 (d, J=8.0 Hz, 1H), 7.35 (s, 1H), 7.18 (d, J=8.0 Hz 2H), 7.09 (d, J=8.4 Hz, 1H), 6.77˜6.79 (m, 1H), 5.00˜5.06 (m, 1H), 3.48˜3.54 (m, 1H), 3.27 (d, J=16.4 Hz, 1H), 2.54˜2.59 (m, 1H), 2.37˜2.44 (m, 1H). MS (M+H)+: 312/314.

Workup

extractionextracted with EA (20 mL×3)
washThe organic layer was washed with brine (30 mL)
dry with materialdried over Na2SO4
concentrationconcentrated
customThe residue was purified by column (PE:EA=1:1)

Sources & evidence

ORD record: ord-87302852fcef4596ba60444d5b199d8f
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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