Methyl iodide → 9-(3-Chloro-4-fluorobenzyl)-7-hydroxy-2-methyl-3,4,10,11-tetrahydro-2H-pyrazino[2,1-a]-2,6-naphthyridine-1,6,8(9H)-trione

HRID 18001Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:19][CH2:18][NH:17][C:16](=[O:20])[C:12]3=2)[C:7]1=[O:23].[H-].[Na+].[CH3:30]I>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]3[CH2:19][CH2:18][N:17]([CH3:30])[C:16](=[O:20])[C:12]3=2)[C:7]1=[O:23]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 9-(3-chloro-4-fluorobenzyl)-7-hydroxy-3,4,10,11-tetrahydro-2-H-pyrazino[2,1-a]-2,6-naphthyridine-1,6,8(9H)-trione (53 mg, 0.14 mmol; Example 5), and sodium hydride (12.3 mg; 60% dispersion in oil) in DMF (2 mL) was stirred at 0° C. for 20 minutes. To the resultant solution, methyl iodide (96 mg, 0.68 mmol) was added and the reaction mixture was heated at 40° C. for four hours. The reaction mixture was quenched with methanol and concentrated under vacuum. The residue was purified by reverse phase high pressure liquid chromatography. Collection and lyophilization of appropriate fractions provided the title compound.

Workup

temperaturethe reaction mixture was heated at 40° C. for four hours
customThe reaction mixture was quenched with methanol
concentrationconcentrated under vacuum
customThe residue was purified by reverse phase high pressure liquid chromatography
customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record: ord-bba0d4c888e8484ea453ad70fd36bfbb
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741315B2

Reaction notes

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