Phosphorus oxychloride → 2-(5-bromopyridine-3-yl)-1-phenyl-1H-benzimidazole

HRID 520824Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:23]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=O.P(Cl)(Cl)(Cl)=O>O1CCOCC1>[Br:1][C:2]1[CH:23]=[C:6]([C:7]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=2)[CH:5]=[N:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Compound 1E (20.0 g, 54.3 mmol) was dissolved in 1,4-dioxane (anhydrous, 150 mL). Phosphorous oxychloride (36 g, 235 mmol) was then added dropwise. The resulting solution was heated at about 100° C. overnight; solids formed. After cooling to RT, the mixture was poured into hexanes (250 mL) to form additional precipitate. Solids were filtered then redissolved in DCM (200 mL) and washed with potassium carbonate (200 mL, saturated solution). The organic phase was collected, dried over sodium sulfate, and loaded onto silica gel. Short silica plug (20% ethyl acetate in hexanes and precipitation from hexanes gave 16.86 g of Compound 1F; 89% yield, pure by HNMR.

Workup

customsolids formed
temperatureAfter cooling to RT
customto form additional precipitate
filtrationSolids were filtered
dissolutionthen redissolved in DCM (200 mL)
washwashed with potassium carbonate (200 mL, saturated solution)
customThe organic phase was collected
dry with materialdried over sodium sulfate
customShort silica plug (20% ethyl acetate in hexanes and precipitation from hexanes

Sources & evidence

ORD record: ord-20b39a85af3e49d2ae7fa92bd31b5f13
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328094B2

Reaction notes

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