Dichloromethane → 2,6-Dimethyl-4-[(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide

HRID 907528Notes

Reaction equation

HRID 907528 reaction equation
[CH3:1][CH:2]1[NH:7][CH:6]([CH3:8])[CH2:5][N:4]([C:9]2[C:13]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)=[N:12][S:11][N:10]=2)[CH2:3]1.ClCCl.C(N(CC)CC)C.[N:32]([C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[C:37]([C:45]([F:48])([F:47])[F:46])[CH:36]=1)=[C:33]=[O:34]>CCOC(C)=O>[F:42][C:41]([F:43])([F:44])[C:39]1[CH:40]=[C:35]([NH:32][C:33]([N:7]2[CH:6]([CH3:8])[CH2:5][N:4]([C:9]3[C:13]([O:14][CH2:15][C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)=[N:12][S:11][N:10]=3)[CH2:3][CH:2]2[CH3:1])=[O:34])[CH:36]=[C:37]([C:45]([F:48])([F:46])[F:47])[CH:38]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 27333143,5-Bis(trifluoromethyl)phenyl isocyanateHCID 590139243,5-Dimethyl-1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine

Product 1

HCID 590138032,6-Dimethyl-4-[(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amideYield 33.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3,5-dimethyl-1-[4-(pyridin-4-ylmethoxy)-[1,2,5]thiadiazol-3-yl]-piperazine (104 mg, 0.34 mmol), dichloromethane (1.0 mL), triethylamine (0.10 mL, 0.43 mmol), and 1-isocyanato-3,5-bis-trifluoromethyl-benzene (0.075 ml, 0.43 mmol) are combined and stirred at room temperature overnight. The reaction mixture was diluted with EtOAc and washed with H2O (1×), sat'd NaHCO3 (2×), 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 63 mg (33%) of 2,6-dimethyl-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) 8.67 (d, 2H), 7.91 (s, 2H), 7.53 (s, 1H), 7.36 (d, 2H), 6.74 (s, 1H), 5.51 (s, 2H), 4.31 (m, 2H), 4.10 (d, 2H), 3.11 (dd, 2H), 1.47 (d, 6H) ppm. LC-MS (MH+)=561.

Workup

  1. washwashed with H2O (1×), sat'd NaHCO3 (2×), sat'd NaCl (1×)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by column chromatography (1:1 hexanes:EtOAc, followed by 1:3 hexanes:EtOAc)

Sources & evidence

ORD record
ord-dff6357929b843ea95e28102ac58b9dc
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Reaction notes

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