Cesium carbonate → 4-Chloro-2-(1-oxo-6,7,8,9-tetrahydropyrazino[1,2-a]indol-2(1H)-yl)nicotinaldehyde

HRID 1021894Notes

Reaction equation

Br[C:2]1[N:9]=[CH:8][CH:7]=[C:6]([Cl:10])[C:3]=1[CH:4]=[O:5].[C:11]1(=[O:24])[C:16]2=[CH:17][C:18]3[CH2:19][CH2:20][CH2:21][CH2:22][C:23]=3[N:15]2[CH:14]=[CH:13][NH:12]1.C(=O)([O-])[O-].[Cs+].[Cs+].COC1C2C(=C3C(=CC=2)C(OC)=CC=N3)N=CC=1>[Cu]I.O1CCOCC1>[Cl:10][C:6]1[C:3]([CH:4]=[O:5])=[C:2]([N:12]2[CH:13]=[CH:14][N:15]3[C:23]4[CH2:22][CH2:21][CH2:20][CH2:19][C:18]=4[CH:17]=[C:16]3[C:11]2=[O:24])[N:9]=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (15 mL), 2-bromo-4-chloronicotinaldehyde 103a (503 mg, 2.28 mmol), 195e (142 mg, 0.76 mmol), cesium carbonate (490 mg, 1.5 mmol), CuI (143 mg, 0.76 mmol), and 4,7-dimethoxy-1,10-phenanthroline (127 mg, 0.52 mmol). After three cycles of vacuum/argon flush, the mixture was heated at 80° C. for 10 hrs. It was then cooled to room temperature and filtered. The filtrate was washed with brine and concentrated under reduced pressure. The resulting residue was purified with silica-gel column chromatography eluting with 1:4 ethyl acetate/petroleum ether to afford 195f (160 mg, 65%) as a yellow solid. MS-ESI: [M+H]+ 328.

Workup

customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
customAfter three cycles of vacuum/argon flush
temperatureIt was then cooled to room temperature
filtrationfiltered
washThe filtrate was washed with brine
concentrationconcentrated under reduced pressure
customThe resulting residue was purified with silica-gel column chromatography
washeluting with 1:4 ethyl acetate/petroleum ether

Sources & evidence

ORD record: ord-ed3c981bade642d6ae08c45d81e189b5
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716274B2

Reaction notes

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