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

HRID 2066143Notes

Reaction equation

HRID 2066143 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:45][C@@H:46]1[NH:51][CH2:50][CH2:49][N:48]([S:52]([C:55]2[CH:60]=[CH:59][C:58]([C:61]([F:64])([F:63])[F:62])=[CH:57][CH:56]=2)(=[O:54])=[O:53])[CH2:47]1>CN(C=O)C>[CH3:1][C:2]1[C:7]([C:8]([N:51]2[CH2:50][CH2:49][N:48]([S:52]([C:55]3[CH:56]=[CH:57][C:58]([C:61]([F:64])([F:62])[F:63])=[CH:59][CH:60]=3)(=[O:53])=[O:54])[CH2:47][C@@H:46]2[CH3:45])=[O:10])=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117152032,6-Dimethylnicotinic acidHCID 59152086(S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazine

Product 1

HCID 59161358(2S)-1-[(2,6-Dimethyl-3-pyridinyl)carbonyl]-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazineYield 65.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,6-Dimethyl-3-pyridinecarboxylic acid (GSK1770624A, Atlantic) (98 mg, 0.65 mmol) and HATU (247 mg, 0.65 mmol) were suspended in DMF (2 ml) and DIPEA (0.170 ml, 0.97 mmol) was added. This mixture was stirred for 40 min at ambient temperature. (3S)-3-Methyl-1-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (may be prepared as described in Description 2) (100 mg, 0.32 mmol) was added and stirring continued for 3 h. The reaction mixture was partitioned between DCM and sat aq. NaHCO3 solution (10 ml each). The layers were separated and the aqueous was washed with further DCM (2×5 ml). The combined organic layers were concentrated to leave a brown oil. This was purified by MDAP to give the title compound (92 mg) as an orange solid.

Workup

  1. stirringstirring
  2. waitcontinued for 3 h
  3. customThe reaction mixture was partitioned between DCM
  4. customThe layers were separated
  5. washthe aqueous was washed with further DCM (2×5 ml)
  6. concentrationThe combined organic layers were concentrated
  7. customto leave a brown oil
  8. customThis was purified by MDAP

Sources & evidence

ORD record
ord-910e23f7f1944a0bbf595dfced06c535
Source dataset
uspto-grants-2012_10
Patent number
US08288388B2

Reaction notes

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