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 2066583Notes

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 mmoH 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-4ffeed3862fb44f999b02844fe53d825
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293731B2

Reaction notes

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