Water → (2S)-2-Methyl-1-[(6-methyl-3-pyridinyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine

HRID 2066116Notes

Reaction equation

HRID 2066116 reaction equation
[CH3:1][C@@H:2]1[NH:7][CH2:6][CH2:5][N:4]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH2:3]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:65][C:66]1[N:71]=[CH:70][C:69]([C:72](O)=[O:73])=[CH:68][CH:67]=1>CN(C=O)C>[CH3:1][C@H:2]1[CH2:3][N:4]([S:8]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:16]=2)(=[O:9])=[O:10])[CH2:5][CH2:6][N:7]1[C:72]([C:69]1[CH:70]=[N:71][C:66]([CH3:65])=[CH:67][CH:68]=1)=[O:73]

Participants

8

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1378606-Methylnicotinic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59152086(S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazine

Product 1

HCID 59161381(2S)-2-Methyl-1-[(6-methyl-3-pyridinyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazineYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S)-3-methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (Description 2) (100 mg, 0.324 mmol) in DMF (5 ml) was added DIPEA (0.170 ml, 0.973 mmol), HOBT.H2O (49.7 mg, 0.324 mmol), HBTU (123 mg, 0.324 mmol) and 6-methyl-3-pyridinecarboxylic acid (44.5 mg, 0.324 mmol) and the reaction mixture was stirred overnight at room temperature. The reaction mixture was evaporated in vacuo, DCM (50 ml) was added and the solution was washed with NaHCO3 (5 ml×2). The organic layer was dried with dried magnesium sulphate which was removed by filtration and the filtrate evaporated to dryness in vacuo. The residual oil was dissolved in 1:1 MeCN/DMSO (1.8 ml) and purified by MDAP in two batches. The fractions containing the desired product were combined and evaporated to dryness in vacuo. The residue was azeotroped with toluene to remove any remaining water to yield the title compound (86 mg).

Workup

  1. customThe reaction mixture was evaporated in vacuo, DCM (50 ml)
  2. additionwas added
  3. washthe solution was washed with NaHCO3 (5 ml×2)
  4. dry with materialThe organic layer was dried with dried magnesium sulphate which
  5. customwas removed by filtration
  6. customthe filtrate evaporated to dryness in vacuo
  7. dissolutionThe residual oil was dissolved in 1:1 MeCN/DMSO (1.8 ml)
  8. custompurified by MDAP in two batches
  9. additionThe fractions containing the desired product
  10. customevaporated to dryness in vacuo
  11. customThe residue was azeotroped with toluene
  12. customto remove any remaining water

Sources & evidence

ORD record
ord-fd088858b9f94d429682f48ca37753de
Source dataset
uspto-grants-2012_10
Patent number
US08288388B2

Reaction notes

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