Sodium Methoxide → 6-(3-chloro-2-methoxypyridin-4-yl)-2-((2S)-2-(4-fluorophenyl) morpholin-4-yl)-3-methyl-3H-pyrimidin-4-one

HRID 1091398Notes

Reaction equation

Cl[C:2]1[C:7]([Cl:8])=[C:6]([C:9]2[N:14]=[C:13]([N:15]3[CH2:20][CH2:19][O:18][C@@H:17]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[CH2:16]3)[N:12]([CH3:28])[C:11](=[O:29])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.[CH3:30][O-:31].[Na+]>O1CCCC1>[Cl:8][C:7]1[C:2]([O:31][CH3:30])=[N:3][CH:4]=[CH:5][C:6]=1[C:9]1[N:14]=[C:13]([N:15]2[CH2:20][CH2:19][O:18][C@@H:17]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[CH2:16]2)[N:12]([CH3:28])[C:11](=[O:29])[CH:10]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A suspension of 6-(2,3-dichloropyridin-4-yl)-2-((2S)-2-(4-fluorophenyl)morpholin-4-yl)-3-methyl-3H-pyrimidin-4-one (0.50 g, 1.15 mmol), and sodium methoxide (1.1 g, 20.4 mmol) in tetrahydrofuran (10 ml) was heated at 60° C. for 5 hours. The resulting suspension was partitioned between chloroform and brine and the aqueous layer was extracted with chloroform. The combined organic layer was washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting 5-10% methanol in chloroform to furnish 6-(3-chloro-2-methoxypyridin-4-yl)-2-((2S)-2-(4-fluorophenyl) morpholin-4-yl)-3-methyl-3H-pyrimidin-4-one (0.27 g, 0.58 mmol, 50%) as white crystals.

Workup

customThe resulting suspension was partitioned between chloroform and brine
extractionthe aqueous layer was extracted with chloroform
washThe combined organic layer was washed with brine
dry with materialdried over magnesium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography
washeluting 5-10% methanol in chloroform

Sources & evidence

ORD record: ord-42f526c4d7b448fa99ee16304e3c9fc9
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129377B2

Reaction notes

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