Diisopropylethylamine → 5-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-ylamino]-[1,3,4]thiadiazole-2-carbonitrile

HRID 1426387Notes

Reaction equation

HRID 1426387 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[S:12][C:11]([C:13]#[N:14])=[N:10][N:9]=2)[CH2:3][CH2:2]1.[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:19]Br.C(N(C(C)C)CC)(C)C>C(#N)C.CN(C)C=O.ClCCl>[F:15][C:16]1[CH:17]=[C:18]([CH:21]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:23]=1)[CH2:19][N:1]1[CH2:2][CH2:3][CH:4]([NH:7][C:8]2[S:12][C:11]([C:13]#[N:14])=[N:10][N:9]=2)[CH2:5][CH2:6]1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27375751-(Bromomethyl)-3-fluoro-5-(trifluoromethyl)benzeneHCID 593235735-(Piperidin-4-ylamino)-[1,3,4]thiadiazole-2-carbonitrile

Product 1

HCID 250549465-[1-(3-Fluoro-5-trifluoromethyl-benzyl)-piperidin-4-ylamino]-[1,3,4]thiadiazole-2-carbonitrileYield 7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(piperidin-4-ylamino)-[1,3,4]thiadiazole-2-carbonitrile (D6) (0.16 g, 0.76 mmol), 3-fluoro-5-(trifluoromethyl)benzyl bromide (0.124 ml, 0.76 mmol) and diisopropylethylamine (0.20 ml, 1.14 mmol) in acetonitrile (2 ml) and N,N-dimethylformamide (0.5 ml) was stirred at room temperature for 48 h. After this period, the reaction mixture was diluted with dichloromethane and extracted with a saturated 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; 2-3% ammonia in methanol (7M)/dichloromethane) to yield E18 (0.019 g, 7%) as a solid. C16H15F4N5S requires 385. Found 386 (MH+).

Workup

  1. waitAfter this period
  2. extractionextracted with a saturated solution of ammonium chloride (25 ml)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. customthe solvent evaporated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica gel; 2-3% ammonia in methanol (7M)/dichloromethane)

Sources & evidence

ORD record
ord-6f5eae4673d244359edee510749b83e0
Source dataset
uspto-grants-2015_01
Patent number
US08933101B2

Reaction notes

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