1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[3-Cyclopropyl-2-(2,6-dichloro-pyridin-4-yl)-3H-imidazol-4-yl]-2-methyl-acrylic acid ethyl ester

HRID 732098Notes

Reaction equation

[CH:1]1([N:4]2[C:8]([CH:9]=O)=[CH:7][N:6]=[C:5]2[C:11]2[CH:16]=[C:15]([Cl:17])[N:14]=[C:13]([Cl:18])[CH:12]=2)[CH2:3][CH2:2]1.C([C:21](CC)(CC)[CH:22](P(O)(O)=O)[C:23]([O-:25])=[O:24])C.[CH2:34]1CCN2C(=NCCC2)C[CH2:35]1>C(#N)C.O>[CH2:34]([O:25][C:23](=[O:24])[C:22]([CH3:21])=[CH:9][C:8]1[N:4]([CH:1]2[CH2:3][CH2:2]2)[C:5]([C:11]2[CH:16]=[C:15]([Cl:17])[N:14]=[C:13]([Cl:18])[CH:12]=2)=[N:6][CH:7]=1)[CH3:35]

Participants

Conditions

Temperature: 78 °C

Procedure

3-cyclopropyl-2-(2,6-dichloro-pyridin-4-yl)-3H-imidazole-4-carbaldehyde (1.48 g, 5.25 mmol), triethyl-2-phosphonopropionate (1.46 ml, 6.83 mmol) and DBU(1.02 ml, 6.83 mmol) were dissolved in acetonitrile (20 ml). After stirring at 78° C. o.n. the reaction mixture was cooled to r.t, diluted with water and extracted with DCM. The combined organic phase was dried (Na2SO4), filtered and concentrated in-vacuo. The crude was purified on silica gel using 6% EA in DCM, and the isolated residue was triturated with hex. to isolate the title compound (1.66 g, 86%). 1H-NMR: 7.86 (m, 1H), 7.75 (d, 2H), 7.43 (s, 1H), 4.34 (q, 2H), 3.45 (m, 1H), 2.19 (s, 3H), 1.39 (t, 3H), 1.29 (m, 2H), 0.78 (m, 2H).

Workup

temperaturethe reaction mixture was cooled
extractionextracted with DCM
dry with materialThe combined organic phase was dried (Na2SO4)
filtrationfiltered
concentrationconcentrated in-vacuo
customThe crude was purified on silica gel using 6% EA in DCM
customthe isolated residue was triturated with hex

Sources & evidence

ORD record: ord-af274af25cc14b2caef46eeeb327f64a
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07585881B2

Reaction notes

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