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

HRID 595734Notes

Reaction equation

[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12][C:13]#N)[N:6]3[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([F:22])[C:20]=4[CH:21]=[C:5]3[C:4]=2[N:3]=1.CC(C[AlH]CC(C)C)C.[OH2:32]>C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[CH2:8][CH:7]([CH2:12][CH:13]=[O:32])[N:6]3[C:15]4[CH:16]=[CH:17][CH:18]=[C:19]([F:22])[C:20]=4[CH:21]=[C:5]3[C:4]=2[N:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 2-(2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)acetonitrile (300 mg, 0.78 mmol) in DCM (6 mL) was stirred at −78° C. for 10 minutes. Then DIBAL-H (1 ml, 1 mmol) was added slowly to the reaction mixture at −78° C. Then the mixture was heated at −78° C. for 2 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=3:1) to afford the desired product of 2-(2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridin-6-yl)acetaldehyde (200 mg, yield: 66%). 1H-NMR (CDCl3, 400 MHz) δ 9.63 (s, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.34 (d, J=9.8 Hz, 1H), 7.11˜7.13 (m, 2H), 7.04 (d, J=8.4 Hz, 1H), 6.75 (t, J=8.0 Hz, 1H), 3.42 (s, 1H), 3.03 (d, J=8.4 Hz, 1H), 2.61˜2.70 (m, 2H). MS (M+H)+: 315/317.

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=3:1)

Sources & evidence

ORD record: ord-64803d6d08a8469e9e7228aef8b87e41
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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