Potassium Carbonate → 4-Chloro-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde

HRID 1022052Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 6,7,8,9-tetrahydropyrido[3,4-b]indolizin-1(2H)-one 112d (1.48 g, 7.9 mmol, 1.0 eq.), 2-bromo-4-chloronicotinaldehyde (3.48 g, 15.8 mmol, 2.0 eq.), CuI (1.50 g, 7.9 mmol, 1.0 eq.), 4,7-dimethoxy-1,10-phenanthroline (2.13 g, 7.9 mmol, 1.0 eq.), K2CO3 (2.18 g, 15.8 mmol, 2.0 eq.) and dioxane (50 mL). The reaction mixture was stirred at 100° C. for 24 h. After the reaction was completed, the mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:2 ethyl acetate/petroleum ether to afford 245a (550 mg, 21%) as a slight yellow solid. MS-ESI: [M+H]+ 328.1.

Workup

customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
filtrationthe mixture was filtered
concentrationthe filtrate was concentrated under reduced pressure
customThe residue was purified by silica-gel column chromatography
washeluting with 1:2 ethyl acetate/petroleum ether

Sources & evidence

ORD record: ord-2ffb52c19ffe4e4d8685dc6af4ea57e7
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08716274B2

Reaction notes

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