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

HRID 43413Notes

Reaction equation

HRID 43413 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[N:31]=[CH:30][C:29]([C:32]([OH:34])=O)=[C:28]([CH3:35])[CH:27]=1.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>[F:25][C:26]1[N:31]=[CH:30][C:29]([C:32]([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:34])=[C:28]([CH3:35])[CH:27]=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 467392746-Fluoro-4-methylpyridine-3-carboxylic acidHCID 59152086(S)-3-Methyl-1-((4-(trifluoromethyl)phenyl)sulfonyl)piperazine

Product 1

HCID 59161361(2S)-1-[(6-Fluoro-4-methyl-3-pyridinyl)carbonyl]-2-methyl-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazineYield 100%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (440 mg, 1.16 mmol) was added to a solution of 6-fluoro-4-methyl-3-pyridinecarboxylic acid (supplied by Frontier Scientific) (150 mg, 0.97 mmol) in DMF (4 ml) and the mixture was treated with DIPEA (0.422 ml, 2.42 mmol). This mixture was stirred for ca. 10 min at ambient temperature. (3S)-3-Methyl-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (may be prepared as described in Description 2) (358 mg, 1.16 mmol) was added and stirring was continued for 1.25 h. The reaction mixture was partitioned between DCM and saturated aqueous NaHCO3 solution (20 ml each). The layers were separated and the aqueous was washed with further DCM (2×20 ml). The combined organic layers were concentrated to leave a dark brown gum. Purification by silica chromatography (Biotage SP4, 25S cartridge), eluting with 12-100% ethyl acetate in hexanes, gave the title compound (432 mg) as a yellow gum.

Workup

  1. stirringstirring
  2. waitwas continued for 1.25 h
  3. customThe reaction mixture was partitioned between DCM and saturated aqueous NaHCO3 solution (20 ml each)
  4. customThe layers were separated
  5. washthe aqueous was washed with further DCM (2×20 ml)
  6. concentrationThe combined organic layers 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 hexanes

Sources & evidence

ORD record
ord-c43982e3f40249539152351f69384b4e
Source dataset
uspto-grants-2013_09
Patent number
US08536183B2

Reaction notes

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