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

HRID 2066128Notes

Reaction equation

HRID 2066128 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.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.[CH3:56][O:57][C:58]1[N:63]=[CH:62][C:61]([C:64](O)=[O:65])=[CH:60][CH:59]=1.CCN(C(C)C)C(C)C>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:64]([C:61]1[CH:62]=[N:63][C:58]([O:57][CH3:56])=[CH:59][CH:60]=1)=[O:65]

Participants

8

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 5924996-Methoxynicotinic 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 59161354(2S)-2-Methyl-1-{[6-(methyloxy)-3-pyridinyl]carbonyl}-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazineYield 59.2%

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 HOBT.H2O (49.7 mg, 0.324 mmol), HBTU (123 mg, 0.324 mmol), 6-(methyloxy)-3-pyridinecarboxylic acid (49.7 mg, 0.324 mmol) and DIPEA (0.170 ml, 0.973 mmol) and the reaction mixture was stirred for 1 h at room temperature. The reaction mixture was evaporated in vacuo. The residue was dissolved in DCM (50 ml), transferred to a separating funnel and the solution was washed with NaHCO3 (5 ml), twice. The organic layer was dried with 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 to yield the title compound (85 mg).

Workup

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

Sources & evidence

ORD record
ord-036dcea67ce14a7186cb91d719129725
Source dataset
uspto-grants-2012_10
Patent number
US08288388B2

Reaction notes

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