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

HRID 1426388Notes

Reaction equation

HRID 1426388 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:27]=[CH:28][C:29]=1[F:30])[CH2:19]N1CCC(N)CC1.C(N(C(C)C)CC)(C)C>C(#N)C.ClCCl>[F:15][C:16]1[CH:17]=[C:18]([CH:27]=[CH:28][C:29]=1[F:30])[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

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 180021391-[(3,4-Difluorophenyl)methyl]piperidin-4-amineHCID 593235735-(Piperidin-4-ylamino)-[1,3,4]thiadiazole-2-carbonitrile

Product 1

HCID 250549475-[1-(3,4-Difluoro-benzyl)-piperidin-4-ylamino]-[1,3,4]thiadiazole-2-carbonitrileYield 25%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-chloro-[1,3,4]thiadiazole-2-carbonitrile (0.3 g, 2.06 mmol) (D6) (prepared by a procedure similar to that described in U.S. Pat. No. 5,736,545), 1-(3,4-difluoro-benzyl)-piperidin-4-ylamine (D7) (0.47 g, 2.06 mmol) and diisopropylethylamine (0.54 ml, 3.09 mmol) in acetonitrile (5 ml) in a sealed tube, was stirred at 80° C. for 1 h., under microwave irradiation. After this period, the reaction mixture was diluted with dichloromethane and extracted with a saturated solution of sodium carbonate (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; 0-2.5% ammonia in methanol (7M)/dichloromethane). The desired fractions were collected and evaporated in vacuo. The crude product was precipitated from acetonitrile to yield E19 (0.17 g, 25%) as a solid. C15H15F2N5S requires 335. Found 336 (MH+).

Workup

  1. customprepared by a procedure similar to
  2. waitAfter this period
  3. extractionextracted with a saturated solution of sodium carbonate (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; 0-2.5% ammonia in methanol (7M)/dichloromethane)
  8. customThe desired fractions were collected
  9. customevaporated in vacuo
  10. customThe crude product was precipitated from acetonitrile

Sources & evidence

ORD record
ord-b001d51222274d30b3f20dea395d10b7
Source dataset
uspto-grants-2015_01
Patent number
US08933101B2

Reaction notes

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