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

HRID 1398307Notes

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]3[CH2:21][CH2:20]3)=[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]3[CH2:21][CH2:20]3)[C:6]=2[CH:5]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of sodium hydride (72.6 mg, 3.03 mmol) in THF (8 mL) at 0° C. was added a solution of 4-(4-chloro-2-fluorophenyl)-N-cyclopropylnicotinamide (440 mg, 1.51 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 another 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 (2×5 mL), dried (Na2SO4) and concentrated under reduced pressure to afford crude 8-chloro-6-cyclopropylbenzo[c][2,7]naphthyridin-5(6H)-one (340 mg, 1.26 mmol, 83% yield) as an off-white solid. LC/MS (ESI) m/e 271.0 [(M+H)+, calcd for C15H12ClN2O 271.1]; LC/MS retention time (method C): tR=1.89 min.

Workup

temperaturewarmed to room temperature
stirringstirred for another 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 (2×5 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-f97775798b3542a99e29a9815a0a88e5
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901305B2

Reaction notes

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