Methyl cyanoacetate → Methyl cyano[6-(methylthio)-4-pyrimidinyl]acetate

HRID 2401184Notes

Reaction equation

[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][CH3:9])=[O:7])#[N:4].[H][H].Cl[C:13]1[CH:18]=[C:17]([S:19][CH3:20])[N:16]=[CH:15][N:14]=1>CS(C)=O>[C:3]([CH:5]([C:13]1[CH:18]=[C:17]([S:19][CH3:20])[N:16]=[CH:15][N:14]=1)[C:6]([O:8][CH3:9])=[O:7])#[N:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of 60% sodium hydride in mineral oil (388 mg, 9.70 mmol) in DMSO (20 mL) was added methyl cyanoacetate (884 mg, 8.92 mmol) at room temperature. After the evolution of hydrogen had ceased, 4-chloro-6-(methylthio)pyrimidine (Intermediate 13, 623 mg, 3.88 mmol) was added. The reaction was heated at 80° C. for 5 hours. The reaction mixtures was then cooled to room temperature and quenched with ice-cooled saturated ammonium chloride solution (50 mL). The solid was filtered and washed with water. Iso-hexane (100 mL) was added to the solid and the resulting mixture was heated at 60° C. for 1 hour and then cooled to room temperature. The solid was filtered and washed with iso-hexane to give the title compound as a yellow solid (700 mg);

Workup

customThe reaction mixtures
temperaturewas then cooled to room temperature
customquenched with ice-
temperaturecooled saturated ammonium chloride solution (50 mL)
filtrationThe solid was filtered
washwashed with water
additionIso-hexane (100 mL) was added to the solid
temperaturethe resulting mixture was heated at 60° C. for 1 hour
temperaturecooled to room temperature
filtrationThe solid was filtered
washwashed with iso-hexane

Sources & evidence

ORD record: ord-fb8f8b3ea54d4d0b87d98491ff744ec0
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796283B2

Reaction notes

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