Diisopropylethylamine → 4-[Methyl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amino]-piperidine-1-carboxylic acid benzyl ester

HRID 1426371Notes

Reaction equation

HRID 1426371 reaction equation
Cl[C:2]1[S:3][C:4]([C:7]([F:10])([F:9])[F:8])=[N:5][N:6]=1.Cl.[CH2:12]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:28][CH3:29])[CH2:24][CH2:23]1)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[CH2:12]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([N:28]([CH3:29])[C:2]2[S:3][C:4]([C:7]([F:10])([F:9])[F:8])=[N:5][N:6]=2)[CH2:24][CH2:23]1)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 132467892-Chloro-5-trifluoromethyl-(1,3,4)thiadiazoleHCID 18621152Benzyl 4-(methylamino)piperidine-1-carboxylate hydrochloride

Product 1

HCID 593235704-[Methyl-(5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)-amino]-piperidine-1-carboxylic acid benzyl esterYield 62%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-5-trifluoromethyl-[1,3,4]thiadiazole (0.70 g, 3.72 mmol) (prepared by a procedure similar to that described in DE 82/3218482), 4-methylamino-piperidine-1-carboxylic acid benzyl ester hydrochloride (1.06 g, 3.72 mmol) and diisopropylethylamine (1.60 ml, 9.30 mmol) in acetonitrile (10 ml) was stirred at 120° C. for 30 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 D1 (0.91 g, 62%) as a solid. C17H19F3N4O2S requires 400. Found 401 (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-fece7749e575415da3de2d77347aab25
Source dataset
uspto-grants-2015_01
Patent number
US08933101B2

Reaction notes

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