Triethylamine → (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-morpholinoethyl)-1H-pyrazol-4-yl]methyl]piperazine dihydrochloride

HRID 584190Notes

Reaction equation

HRID 584190 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18](CCO)[CH:19]=2)[CH2:10][C@H:9]1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=1)=[O:7].[CH2:41]([N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])[CH3:42].CS([Cl:52])(=O)=[O:50]>C(OCC)(=O)C>[ClH:52].[ClH:52].[F:37][C:35]([F:38])([F:36])[C:33]1[CH:32]=[C:5]([CH:4]=[C:3]([C:2]([F:39])([F:1])[F:40])[CH:34]=1)[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[N:17][N:18]([CH2:42][CH2:41][N:43]3[CH2:46][CH2:47][O:50][CH2:45][CH2:44]3)[CH:19]=2)[CH2:10][C@H:9]1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=1)=[O:7]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 54495194(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine

Product 1

HCID 86596427(2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-morpholinoethyl)-1H-pyrazol-4-yl]methyl]piperazine dihydrochloride

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]methyl]piperazine (152 mg) in ethyl acetate (2 ml) was added triethylamine (0.048 ml) and methanesulfonyl chloride (0.027 ml) at room temperature. After stirring for 10 minutes, the mixture was quenched with water and extracted with ethyl acetate. The combined extracts were washed with water and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure. The obtained residue was dissolved with N,N-dimethylformamide (2 ml) and added morpholine (0.028 ml), potassium carbonate (74 mg) and potassium iodide (13 mg). After stirring at 70° C. for 6 hours, the mixture was quenched with water and extracted with ethyl acetate. The combined extracts were washed with water and brine successively, dried over magnesium sulfate, and evaporated under reduced pressure. The obtained residue was dissolved in ethyl acetate and treated with 4N hydrogen chloride in ethyl acetate (0.2 ml) at room temperature. The mixture was added hexane, filtered, and dried over reduced pressure to give (2R)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(3,4-dimethylbenzyl)-4-[[1-(2-morpholinoethyl)-1H-pyrazol-4-yl]methyl]piperazine dihydrochloride (188.7 mg) as a solid.

Workup

  1. customthe mixture was quenched with water
  2. extractionextracted with ethyl acetate
  3. washThe combined extracts were washed with water and brine successively
  4. dry with materialdried over magnesium sulfate
  5. customevaporated under reduced pressure
  6. dissolutionThe obtained residue was dissolved with N,N-dimethylformamide (2 ml)
  7. additionadded morpholine (0.028 ml), potassium carbonate (74 mg) and potassium iodide (13 mg)
  8. stirringAfter stirring at 70° C. for 6 hours
  9. customthe mixture was quenched with water
  10. extractionextracted with ethyl acetate
  11. washThe combined extracts were washed with water and brine successively
  12. dry with materialdried over magnesium sulfate
  13. customevaporated under reduced pressure
  14. dissolutionThe obtained residue was dissolved in ethyl acetate
  15. additiontreated with 4N hydrogen chloride in ethyl acetate (0.2 ml) at room temperature
  16. additionThe mixture was added hexane
  17. filtrationfiltered
  18. customdried over reduced pressure

Sources & evidence

ORD record
ord-b3aa2d98cbba4009b000dbcb1371fa15
Source dataset
uspto-grants-2005_08
Patent number
US06924278B2

Reaction notes

Loading…