4-Fluorobenzyl chloride → [1-(4-Fluoro-benzyl)-piperidin-4-yl]-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine

HRID 1426382Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:9][C:10]([C:13]([F:16])([F:15])[F:14])=[N:11][N:12]=2)[CH2:3][CH2:2]1.[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Cl)=[CH:20][CH:19]=1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][N:1]2[CH2:6][CH2:5][CH:4]([NH:7][C:8]3[S:9][C:10]([C:13]([F:16])([F:14])[F:15])=[N:11][N:12]=3)[CH2:3][CH2:2]2)=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine (D4) (0.040 g, 0.16 mmol), 4-fluorobenzyl chloride (0.023 ml, 0.19 mmol) and diisopropylethylamine (0.042 ml, 0.24 mmol) in acetonitrile (3 ml) was stirred at 120° C. for 30 min., under microwave irradiation. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and extracted with a 10% solution of ammonium chloride (25 ml). The organic layer was separated, dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 0-3% ammonia in methanol (7M)/dichloromethane) to yield E4 (0.042 g, 73%) as a solid. C15H16F4N4S requires 360. Found 361 (MH+).

Workup

temperatureAfter cooling to room temperature
extractionextracted with a 10% solution of ammonium chloride (25 ml)
customThe organic layer was separated
dry with materialdried (Na2SO4)
customthe solvent evaporated in vacuo
customThe crude product was purified by flash column chromatography (silica gel; 0-3% ammonia in methanol (7M)/dichloromethane)

Sources & evidence

ORD record: ord-afbbb94f430341bc885eaf9bc3c299cd
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933101B2

Reaction notes

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