Cesium carbonate → 3-Bromo-5-(1-oxo-3,4,6,7,8,9-hexahydropyrido[3,4-b]indolizin-2(1H)-yl)isonicotinaldehyde

HRID 592565Notes

Reaction equation

Br[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([Br:10])[C:3]=1[CH:4]=[O:5].[C:11]1(=[O:24])[C:16]2[CH:17]=[C:18]3[N:23]([C:15]=2[CH2:14][CH2:13][NH:12]1)[CH2:22][CH2:21][CH2:20][CH2:19]3.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:10][C:6]1[CH:7]=[N:8][CH:9]=[C:2]([N:12]2[CH2:13][CH2:14][C:15]3[N:23]4[C:18]([CH2:19][CH2:20][CH2:21][CH2:22]4)=[CH:17][C:16]=3[C:11]2=[O:24])[C:3]=1[CH:4]=[O:5]

Participants

Conditions

Temperature: 100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (15 mL), 3,5-dibromoisonicotinaldehyde (400 mg, 1.5 mmol), 112d (142 mg, 0.76 mmol) and cesium carbonate (176 mg, 1.5 mmol). Xantphos (40 mg, 0.08 mmol) and Pd2(dba)3 (70 mg, 0.08 mmol) were added, and the reaction mixture was heated at 100° C. for 5 h. After this time the reaction was cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on flash column eluting with DCM:MeOH (20:1) to afford 112e (200 mg, 70%). MS: [M+H]

Workup

customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
temperaturereflux condenser
temperatureAfter this time the reaction was cooled to room temperature
filtrationfiltered
concentrationThe filtrate was concentrated under reduced pressure
customthe residue was purified on flash column
washeluting with DCM:MeOH (20:1)

Sources & evidence

ORD record: ord-07c9ed60cc6c4b0ba728a0bd3eea25b7
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238655B2

Reaction notes

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