Diisopropylethylamine → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4,4,4-trifluoro-butyryl]-piperazine-1-carboxylic acid propyl ester

HRID 1970656Notes

Reaction equation

HRID 1970656 reaction equation
[CH:1]1([NH:5][C:6]([C@@H:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13](=[O:30])[CH2:14][O:15][C:16]2[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:19]=[C:18]([C:27](O)=[O:28])[CH:17]=2)=[O:7])[CH2:4][CH2:3][CH2:2]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.[CH2:64]([O:67][C:68]([N:70]1[CH2:75][CH2:74][N:73]([C:76](=[O:84])[C@@H:77]([NH2:83])[CH2:78][C:79]([F:82])([F:81])[F:80])[CH2:72][CH2:71]1)=[O:69])[CH2:65][CH3:66].C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:64]([O:67][C:68]([N:70]1[CH2:75][CH2:74][N:73]([C:76](=[O:84])[C@@H:77]([NH:83][C:27]([C:18]2[CH:17]=[C:16]([O:15][CH2:14][C:13]([N:9]3[CH2:10][CH2:11][CH2:12][C@H:8]3[C:6](=[O:7])[NH:5][CH:1]3[CH2:4][CH2:3][CH2:2]3)=[O:30])[N:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:19]=2)=[O:28])[CH2:78][C:79]([F:80])([F:82])[F:81])[CH2:72][CH2:71]1)=[O:69])[CH2:65][CH3:66]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 668546174-((S)-2-Amino-4,4,4-trifluoro-butyryl)-piperazine-1-carboxylic acid propyl esterHCID 668546955-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 668551994-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-4,4,4-trifluoro-butyryl]-piperazine-1-carboxylic acid propyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 100 mg 5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 3 ml DMF were added 92 mg HATU, 82 l DIPEA and 75 mg 4-((S)-2-Amino-4,4,4-trifluoro-butyryl)-piperazine-1-carboxylic acid propyl ester. After stirring for 3 h saturated NaHCO3 solution (1.5 ml) was added and the mixture passed through a Chem Elute® cartridge eluting with DCM. The crude product obtained after evaporation of the solvent was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give the title compound.

Workup

  1. additionwas added
  2. washElute® cartridge
  3. washeluting with DCM
  4. customThe crude product obtained
  5. customafter evaporation of the solvent
  6. customwas purified by preparative HPLC (
  7. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-f6517447a89f4209858c16ad32ee0dde
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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