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

HRID 43415Notes

Reaction equation

HRID 43415 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-3fb4c1accc7f4eaeb716522d44c4ca20
Source dataset
uspto-grants-2013_09
Patent number
US08536183B2

Reaction notes

Loading…