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

HRID 1426381Notes

Reaction equation

[CH3:1][N:2]([CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)[C:3]1[S:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][N:7]=1.[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]Br.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][N:15]1[CH2:16][CH2:17][CH:12]([N:2]([CH3:1])[C:3]2[S:4][C:5]([C:8]([F:11])([F:9])[F:10])=[N:6][N:7]=2)[CH2:13][CH2:14]1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of methyl-piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine (D2) (0.050 g, 0.19 mmol), 3-fluorobenzyl bromide (0.030 ml, 0.24 mmol) and diisopropylethylamine (0.050 ml, 0.28 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; 0-1.5% ammonia in methanol (7M)/dichloromethane) to yield E2 (0.062 g, 88%) as a solid. C16H18F4N4S requires 374. Found 375 (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; 0-1.5% ammonia in methanol (7M)/dichloromethane)

Sources & evidence

ORD record: ord-f864752e589e457a9b17917bceabb696
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933101B2

Reaction notes

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