Triethylamine → 4-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide

HRID 907524Notes

Reaction equation

HRID 907524 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][C:6]([CH2:9][O:10][C:11]2[C:12]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[N:13][S:14][N:15]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[N:29]([C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[C:34]([C:42]([F:45])([F:44])[F:43])[CH:33]=1)=[C:30]=[O:31]>ClCCl.CCOC(C)=O>[F:39][C:38]([F:40])([F:41])[C:36]1[CH:37]=[C:32]([NH:29][C:30]([N:19]2[CH2:20][CH2:21][N:16]([C:12]3[C:11]([O:10][CH2:9][C:6]4[CH:7]=[CH:8][N:3]=[CH:4][CH:5]=4)=[N:15][S:14][N:13]=3)[CH2:17][CH2:18]2)=[O:31])[CH:33]=[C:34]([C:42]([F:45])([F:43])[F:44])[CH:35]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 1317291731-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine, dihydrochloride salt

Product 1

HCID 98717044-[4-(Pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amideYield 80%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine, dihydrochloride salt (2.13 g, 6.1 mmol), dichloromethane (40 mL), and triethylamine (2.5 mL, 17.9 mmol) were combined and cooled in an icebath. 1-Isocyanato-3,5-bis-trifluoromethyl-benzene (1.89 g, 7.4 mmol) in dichloromethane (10 mL) was added dropwise and the resulting mixture stirred overnight at room temperature. The reaction mixture was diluted with EtOAc and washed with sat'd NaHCO3 (3×), sat'd NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product was purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc) to give 2.6 g (80%) of 4-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide as a white solid after lyophilization from: H2O—AcCN. 1H NMR (CDCl3) 8.62 (d, 2H), 7.84 (s, 2H), 7.50 (s, 1H), 7.31 (d, 2H), 7.06 (s, 1H), 5.49 (s, 2H), 3.68-3.60 (m, 8H) ppm. LC-MS (MH+)=533.

Workup

  1. temperaturecooled in an icebath
  2. washwashed with sat'd NaHCO3 (3×), sat'd NaCl (1×)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-6f4fb1f918544edd8a1f6fa8ad468232
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Reaction notes

Loading…