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

HRID 1970575Notes

Reaction equation

HRID 1970575 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:82])[CH:77]([NH2:81])[CH:78]([F:80])[CH3:79])[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:82])[CH:77]([NH:81][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])[CH:78]([F:80])[CH3:79])[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 668545724-(2-Amino-3-fluoro-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 668559104-[2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-3-fluoro-butyryl]-piperazine-1-carboxylic acid propyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 150 mg 5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acid in 4 ml DMF were added 138 mg HATU, 124 l DIPEA and 100 mg 4-(2-Amino-3-fluoro-butyryl)-piperazine-1-carboxylic acid propyl ester. After stirring for 12 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-5158ecf142834390b3d7e4e7137ae07c
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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