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

HRID 220076Notes

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>[CH3:9][O:8][C:6](=[O:7])[CH:5]([C:3]#[N:4])[C:13]1[CH:18]=[C:17]([S:19][CH3:20])[N:16]=[CH:15][N:14]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To the suspension of NaH (2.19 g, 55 mmol, 60% in oil) in DMSO (20 mL) is added methyl cyanoacetate (4.88 mL, 51 mmol) at 23° C. (cooled by ice-water if necessary). After the evolution of hydrogen has ceased, 4-chloro-6-methylsulfanyl-pyrimidine (3.56 g, 22 mmol) is added. The reaction is heated at 80° C. for 5 hours. The reaction mixture is then cooled to room temperature and quenched with ice-cooled saturated NH4Cl (50 mL). The solid is filtered and washed with water. 100 mL of hexanes is added to the solid and heated at 60° C. for 1 hour and then cooled to room temperature. The solid is filtered and washed with hexanes to afford cyano-(6-methylsulfanyl-pyrimidin-4-yl)-acetic acid methyl ester. 1H NMR 400 MHz (d6-DMSO) δ 8.42 (d, 1H), 6.64 (s, 1H), 3.71 (s, 3H), 2.55 (s, 3H). MS m/z 224.10 (M+1).

Workup

temperatureThe reaction mixture is then cooled to room temperature
customquenched with ice-
temperaturecooled saturated NH4Cl (50 mL)
filtrationThe solid is filtered
washwashed with water
addition100 mL of hexanes is added to the solid
temperatureheated at 60° C. for 1 hour
temperaturecooled to room temperature
filtrationThe solid is filtered
washwashed with hexanes

Sources & evidence

ORD record: ord-cd706135ff9a48f5a4b8aea70b197eaf
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202876B2

Reaction notes

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