Sodium hydride → 8-chloro-6-isopropylbenzo[c][2,7]naphthyridin-5(6H)-one

HRID 1398303Notes

Reaction equation

[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:15]([C:16]([NH:18][CH:19]([CH3:21])[CH3:20])=[O:17])=[CH:14][N:13]=[CH:12][CH:11]=2)=[C:6](F)[CH:5]=1>C1COCC1>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]2[C:10]3[C:15](=[CH:14][N:13]=[CH:12][CH:11]=3)[C:16](=[O:17])[N:18]([CH:19]([CH3:21])[CH3:20])[C:6]=2[CH:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of sodium hydride (79 mg, 3.28 mmol) in THF (8 mL) at 0° C. was added a solution of 4-(4-chloro-2-fluorophenyl)-N-isopropylnicotinamide (480 mg, 1.640 mmol) in THF (10 mL) dropwise over a period of 10 min. The reaction mixture was stirred at 0° C. for 1 h and then warmed to room temperature and stirred for an additional 1 h. The reaction mixture was then treated with ice and extracted with ethyl acetate (3×5 mL). The combined organic layers were washed with brine (1×5 mL), dried (Na2SO4) and concentrated under reduced pressure to afford crude 8-chloro-6-isopropylbenzo[c][2,7]naphthyridin-5(6H)-one (250 mg, 0.917 mmol, 56% yield). LC/MS (ESI) m/e 273.0 [(M+H)+, calcd for C15H14ClN2O 273.1]; LC/MS retention time (method C): tR=1.98 min; 1H NMR (400 MHz, CDCl3) δ ppm 9.67 (s, 1H), 8.70 (d, J=6.0 Hz, 1H), 8.17-8.19 (d, J=8.4 Hz, 1H), 7.92-7.94 (d, J=5.6 Hz, 1H), 7.62 (d, J=1.6 Hz, 1H), 7.26-7.31 (dd, J=8.8, 2.0 Hz, 1H), 3.21-3.28 (m, 1H), 1.71 (d, J=6.8 Hz, 6H).

Workup

temperaturewarmed to room temperature
stirringstirred for an additional 1 h
additionThe reaction mixture was then treated with ice
extractionextracted with ethyl acetate (3×5 mL)
washThe combined organic layers were washed with brine (1×5 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-ae45718455a54afea34d7c115e57e572
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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