Triethylamine → (E)-ethyl-3-(4-(ethylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl)acrylate

HRID 1893881Notes

Reaction equation

[CH2:1]([NH:3][C:4]1[C:9](I)=[C:8]([CH3:11])[N:7]=[C:6]([S:12][CH3:13])[N:5]=1)[CH3:2].[C:14]([O:18][CH2:19][CH3:20])(=[O:17])[CH:15]=[CH2:16].C(N(CC)CC)C>CC(N(C)C)=O.C(OCC)(=O)C.CCCCCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:19]([O:18][C:14](=[O:17])/[CH:15]=[CH:16]/[C:9]1[C:4]([NH:3][CH2:1][CH3:2])=[N:5][C:6]([S:12][CH3:13])=[N:7][C:8]=1[CH3:11])[CH3:20]

Participants

Conditions

Temperature: 100 °C

Procedure

To the solution of N-ethyl-5-iodo-6-methyl-2-(methylthio)pyrimidin-4-amine (25.2 g, 81.48 mmol) in DMA (260 mL) were added ethyl acrylate (12.23 g, 122.2 mmol), Pd(OAc)2 (3.65 g, 16.25 mmol), (+)BINAP and triethyl amine (24.68 g, 244.4 mmol). Then the reaction mixture was heated to 100° C. and reacted overnight. After evaporation of solvent, the residue was diluted with water and the aqueous layer was extracted with ethyl acetate. The product (E)-ethyl-3-(4-(ethylamino)-6-methyl-2-(methylthio)pyrimidin-5-yl)acrylate (16.8 g, 73% yield) was isolated by silica gel column chromatography with 6-8% ethyl acetate in hexane as eluent. 1H NMR (400 MHz, CDCl3): δ 7.65 (d, J=16.4 Hz, 1H), 6.20 (d, J=16.4 Hz, 1H), 5.15 (bs, 1H), 4.28 (q, J=7.2 Hz, 2H), 3.54 (q, J=7.2 Hz, 2H), 2.53 (s, 3H), 2.37 (s, 3H), 1.35 (t, J=7.2 Hz, 3H), 1.24 (t, J=7.2 Hz, 3H).

Workup

customreacted overnight
customAfter evaporation of solvent
additionthe residue was diluted with water
extractionthe aqueous layer was extracted with ethyl acetate

Sources & evidence

ORD record: ord-b85a03e9943b4fb491e6ad43f912ce8f
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513266B2

Reaction notes

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