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

HRID 1426373Notes

Reaction equation

HRID 1426373 reaction equation
Cl[C:2]1[S:3][C:4]([C:7]([F:10])([F:9])[F:8])=[N:5][N:6]=1.NC[CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:15][CH2:14]1.C([N:29](C(C)C)CC)(C)C>C(#N)C.ClCCl>[CH2:19]([N:16]1[CH2:17][CH2:18][CH:13]([NH:29][C:2]2[S:3][C:4]([C:7]([F:10])([F:9])[F:8])=[N:5][N:6]=2)[CH2:14][CH2:15]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514444(1-Benzyl-4-piperidyl)methanamineHCID 132467892-Chloro-5-trifluoromethyl-(1,3,4)thiadiazole

Product 1

HCID 25055179(1-Benzyl-piperidin-4-yl)-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amineYield 55.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-5-trifluoromethyl-[1,3,4]thiadiazole (0.42 g, 2.24 mmol) (prepared by a procedure similar to that described in DE 82/3218482), 4-aminomethyl-1-benzylpiperidine (0.4 ml, 1.95 mmol) and diisopropylethylamine (0.5 ml, 2.90 mmol) in acetonitrile (6 ml) was stirred at 120° C. for 15 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 short open column chromatography (silica gel; 0-0.5% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo to yield D3 (0.368 g, 48%) as a solid. C15H17F3N4S requires 342. Found 343 (MH+).

Workup

  1. customprepared by a procedure similar to
  2. temperatureAfter cooling to room temperature
  3. extractionextracted with a 10% solution of ammonium chloride (25 ml)
  4. customThe organic layer was separated
  5. dry with materialdried (Na2SO4)
  6. customthe solvent evaporated in vacuo
  7. customThe crude product was purified by short open column chromatography (silica gel; 0-0.5% ammonia in methanol (7M)/dichloromethane)
  8. customThe desired fractions were collected
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-4b8f2dd829ca4b00b8fd5cc44061d6e5
Source dataset
uspto-grants-2015_01
Patent number
US08933101B2

Reaction notes

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