Diisopropylethylamine → (2S)-1-[(4-Chloro-2-pyridinyl)carbonyl]-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine

HRID 41318Notes

Reaction equation

HRID 41318 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[CH:31]=[CH:30][N:29]=[C:28]([C:32]([OH:34])=O)[CH:27]=1.CCN(C(C)C)C(C)C.[CH3:44][C@@H:45]1[NH:50][CH2:49][CH2:48][N:47]([S:51]([C:54]2[CH:59]=[CH:58][C:57]([C:60]([F:63])([F:62])[F:61])=[CH:56][CH:55]=2)(=[O:53])=[O:52])[CH2:46]1>CN(C=O)C>[Cl:25][C:26]1[CH:31]=[CH:30][N:29]=[C:28]([C:32]([N:50]2[CH2:49][CH2:48][N:47]([S:51]([C:54]3[CH:55]=[CH:56][C:57]([C:60]([F:63])([F:61])[F:62])=[CH:58][CH:59]=3)(=[O:52])=[O:53])[CH2:46][C@@H:45]2[CH3:44])=[O:34])[CH:27]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2308904-Chloropyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59152086(S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazine

Product 1

HCID 44612194(2S)-1-[(4-Chloro-2-pyridinyl)carbonyl]-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazineYield 39.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (411 mg, 1.08 mmol) was added to a solution of 4-chloro-2-pyridinecarboxylic acid (142 mg, 0.90 mmol) in DMF (4 ml) and the mixture was treated with DIPEA (0.394 ml, 2.25 mmol). This mixture was stirred for ca. 10 min at ambient temperature. (3S)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (Description 2) (333 mg, 1.082 mmol) was then added and stirring was continued for 1.5 h. The reaction mixture was partitioned between DCM and sat aq. NaHCO3 solution (20 ml each). The layers were separated and the aqueous was washed with further DCM (2×20 ml). The combined organics were concentrated to leave a dark brown gum. Purification by silica chromatography (Biotage SP4, 25S cartridge), eluting with 12-100% ethyl acetate in isohexane, gave a pale yellow gum, shown to be impure by LCMS and NMR analysis. Further purification by MDAP gave the title compound as a colourless glass (159 mg).

Workup

  1. stirringstirring
  2. waitwas continued for 1.5 h
  3. customThe reaction mixture was partitioned between DCM
  4. customThe layers were separated
  5. washthe aqueous was washed with further DCM (2×20 ml)
  6. concentrationThe combined organics were concentrated
  7. customto leave a dark brown gum
  8. customPurification by silica chromatography (Biotage SP4, 25S cartridge)
  9. washeluting with 12-100% ethyl acetate in isohexane
  10. customgave a pale yellow gum
  11. customFurther purification by MDAP

Sources & evidence

ORD record
ord-16803ae8237d45ae98377427f829d7ab
Source dataset
uspto-grants-2013_09
Patent number
US08530478B2

Reaction notes

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