Sodium hydride → 8-(4-Methoxybenzyl)-6-bromo-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 472210Notes

Reaction equation

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

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of sodium hydride (60% dispersion in mineral oil) (90 mg, 1.5 equiv.) and anhydrous DMF (5 mL) was added 6-bromo-4-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (429 mg, 1.5 mmol) and the mixture stirred for 30 minutes at 50° C. Solution was then cooled a little and p-methoxybenzylchloride (281 mg, 1.2 equiv) in 1 mL DMF was then added dropwise. Heated to 50° C. for 3 hours and then stirred at rt overnight. Cooled to rt, partitioned between water and AcOEt, water further washed with AcOEt, pooled organic extracts washed with saturated sodium bicarbonate, brine and dried over MgSO4. Filtration and solvent removal afforded crude material which was used without further purification. Yield 675 mg.

Workup

additionwas then added dropwise
temperatureHeated to 50° C. for 3 hours
stirringstirred at rt overnight
temperatureCooled to rt
custompartitioned between water and AcOEt, water
washfurther washed with AcOEt
washwashed with saturated sodium bicarbonate, brine
dry with materialdried over MgSO4
filtrationFiltration and solvent removal
customafforded crude material which
customwas used without further purification

Sources & evidence

ORD record: ord-24402aefbc314ba99f97c28711496205
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08633204B2

Reaction notes

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