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

HRID 1426384Notes

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[CH3:26])[CH2:21]Br.N12CCCNC1=NCCC2>C(#N)C>[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[CH3:26])[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: 80 °C

Procedure

A mixture of piperidin-4-yl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amine (D4) (0.025 g, 0.1 mmol), 3-fluoro-4-methylbenzyl bromide (0.012 ml, 0.11 mmol) and polymer supported 1,5,7-triazabicyclo[4.4.0]dec-5-ene (2.9 mmol/g) (0.102 g, 0.30 mmol) in acetonitrile (3 ml) was stirred at 80° C. for 30 min. After cooling to room temperature, the reaction mixture was filtered through an Isolute SCX-2 cartridge. The cartridge was then washed with methanol. The crude product was eluted with a 7M solution of ammonia in methanol. The solvent was evaporated in vacuo. The crude product was purified by flash column chromatography (silica gel; 5% ammonia in methanol (7M)/dichloromethane) to yield E9 (0.017 g, 45%) as a solid. C16H18F4N4S requires 374. Found 375 (MH+).

Workup

temperatureAfter cooling to room temperature
filtrationthe reaction mixture was filtered through an Isolute SCX-2 cartridge
washThe cartridge was then washed with methanol
washThe crude product was eluted with a 7M solution of ammonia in methanol
customThe solvent was evaporated in vacuo
customThe crude product was purified by flash column chromatography (silica gel; 5% ammonia in methanol (7M)/dichloromethane)

Sources & evidence

ORD record: ord-d2f0d658ea3840c69315bdb6f6849660
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933101B2

Reaction notes

Loading…