Acetic Acid → HCID 86651293, compound

HRID 1921233Notes

Reaction equation

[CH:1]([C:3]1[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])[N:7]2[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]2)=O.[Cl-].[Cl:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[CH2:27][NH2+:26][CH2:25][CH2:24]2.C(O)(=O)C.C([BH3-])#N>ClC(Cl)C.C(N(CC)CC)C>[Cl:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[CH2:27][N:26]([CH2:1][C:3]1[CH:4]=[C:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6](=[O:13])[N:7]3[C:12]=1[CH:11]=[CH:10][CH:9]=[CH:8]3)[CH2:25][CH2:24]2

Participants

Conditions

Temperature: 120 °C

Procedure

Ethyl 1-formyl-4-oxo-4H-quinolizine-3-carboxylate (300 mg, 1.22 mmol) and 6-chloro-1,2,3,4-tetrahydroisoquinolinium chloride (267 mg, 1.59 mmol) were dissolved in 6.2 mL of dichloroethane, and the reaction was neutralized by adding triethylamine dropwise to reach pH 7. The reaction mixture was re-acidified by adding glacial acetic acid (420 μl, 7.34 mmol). MP-Cyanoborohydride resin (1 spatula tip, excess) was added, and the reaction was stirred and heated at 120° C. for 20 minutes in a Emrys Optimizer™ microwave. The crude reaction mixture was filtered with methanol, concentrated in vacuo and redissolved in dimethylsulfoxide, then was purified by reverse phase HPLC, eluting with 20-90% acetonitrile in water to afford ethyl 1-[(6-chloro-3,4-dihydroisoquinolin-2(1H)-yl)methyl]-4-oxo-4H-quinolizine-3-carboxylate that gave a proton NMR spectrum consistent with theory and a mass ion (ES+) of 397.0.

Workup

customThe crude reaction mixture
filtrationwas filtered with methanol
concentrationconcentrated in vacuo
dissolutionredissolved in dimethylsulfoxide
customwas purified by reverse phase HPLC
washeluting with 20-90% acetonitrile in water

Sources & evidence

ORD record: ord-1351c3269f0b4f6e9261e8a65091c077
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173672B2

Reaction notes

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