Diisopropylethylamine → 1-[2-(5,6-Difluorobenzimidazol-2-ylthio)ethyl]-4-formylpiperazine

HRID 1354252Notes

Reaction equation

[CH:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][CH2:10]O)[CH2:5][CH2:4]1)=[O:2].[F:12][C:13]1[C:22]([F:23])=[CH:21][C:16]2[N:17]=[C:18]([SH:20])[NH:19][C:15]=2[CH:14]=1.C(N(C(C)C)CC)(C)C.[I-].C(C[P+](C)(C)C)#N>C(#N)CC.O>[F:23][C:22]1[C:13]([F:12])=[CH:14][C:15]2[N:19]=[C:18]([S:20][CH2:10][CH2:9][N:6]3[CH2:7][CH2:8][N:3]([CH:1]=[O:2])[CH2:4][CH2:5]3)[NH:17][C:16]=2[CH:21]=1

Participants

Conditions

Temperature: 92 °C

Procedure

1-Formyl-4-(2-hydroxyethyl)piperazine (1.11 g, 7.0 mmol), 5,6-difluoro-2-mercaptobenzimidazole (1.30 g, 7.0 mmol), and diisopropylethylamine (3.62 g, 28.0 mmol) were dissolved in propionitrile (50 mL), and cyanomethyltrimethylphosphonium iodide (6.80 g, 28.0 mmol) was added thereto, followed by stirring for one hour at 92° C. under argon. The reaction mixture was allowed to cool and then poured in water (100 mL), followed by extraction with chloroform (100 mL×3). The organic layer was washed with saturated brine and then dried over sodium sulfate anhydrate, and the product was concentrated under reduced pressure. The crude product was crystallized from acetone-ether, to thereby yield 1-[2-(5,6-difluorobenzimidazol-2-ylthio)ethyl]-4-formylpiperazine (1.78 g, yield 78%) as a yellow crystalline powder.

Workup

temperatureto cool
extractionfollowed by extraction with chloroform (100 mL×3)
washThe organic layer was washed with saturated brine
dry with materialdried over sodium sulfate anhydrate
concentrationthe product was concentrated under reduced pressure
customThe crude product was crystallized from acetone-ether

Sources & evidence

ORD record: ord-b548b0fb1a1f4bff9e20d0bb3e68ea7c
Source dataset: uspto-grants-2007_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07223764B2

Reaction notes

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