Diisopropylethylamine → [1-(3,4-Difluoro-benzyl)-piperidin-4-yl]-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine

HRID 1426383Notes

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:19]=[C:20]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:21]Br.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[F:26])[CH2:21][N:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:9][C:10]([C:13]([F:16])([F:14])[F:15])=[N:11][N:12]=2)[CH2:3][CH2:2]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine (D4) (0.040 g, 0.16 mmol), 3,4-difluorobenzyl bromide (0.024 ml, 0.19 mmol) and diisopropylethylamine (0.042 ml, 0.24 mmol) in acetonitrile (3 ml) was stirred at 100° C. for 5 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 E5 (0.048 g, 80%) as a solid. C15H15F5N4S requires 378. Found 379 (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-dca8276863824755988a350dd6f2ab8c
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933101B2

Reaction notes

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