Cesium carbonate → 3-[1-ethyl-5-(4-isopropylphenoxy)-1H-pyrazol-3-yl]benzonitrile

HRID 540760Notes

Reaction equation

[CH2:1]([N:3]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])[NH:4]1)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O.Br[C:32]1[CH:37]=[CH:36][C:35]([CH:38]([CH3:40])[CH3:39])=[CH:34][CH:33]=1>[Cu]I.O1CCOCC1>[CH2:1]([N:3]1[C:7]([O:8][C:32]2[CH:37]=[CH:36][C:35]([CH:38]([CH3:40])[CH3:39])=[CH:34][CH:33]=2)=[CH:6][C:5]([C:9]2[CH:10]=[C:11]([CH:14]=[CH:15][CH:16]=2)[C:12]#[N:13])=[N:4]1)[CH3:2]

Participants

Conditions

Temperature: 110 °C

Procedure

Dioxane (4.7 mL) was added to a mixture of 3-(1-ethyl-5-oxo-2,5-dihydro-1H-pyrazol-3-yl)benzonitrile (500 mg, 2.35 mmol, 1 equiv), cesium carbonate (1.53 g, 4.69 mmol, 2.00 equiv), copper (I) iodide (112 mg, 0.586 mmol, 0.250 equiv) and N,N-dimethylglycine hydrochloride (164 mg, 1.17 mmol, 0.50 equiv). The reaction flask was sealed, and nitrogen gas was bubbled through the reaction mixture for 5 minutes with a needle. The needle was removed, and 1-bromo-4-isopropylbenzene (934 mg, 4.69 mmol, 2.00 equiv) was added. The reaction flask was sealed and heated to 110° C. for 16 hours. The crude reaction mixture was loaded directly onto a silica gel column and purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes) to afford 3-[1-ethyl-5-(4-isopropylphenoxy)-1H-pyrazol-3-yl]benzonitrile (165 mg, 21%). Calcd (M+1)+: 332.2. Found: 332.1.

Workup

customThe reaction flask was sealed
customnitrogen gas was bubbled through the reaction mixture for 5 minutes with a needle
customThe needle was removed
customThe reaction flask was sealed
customThe crude reaction mixture
custompurified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record: ord-f10a0a144be147f390a0bb6faf54341c
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08871796B2

Reaction notes

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