Diisopropylethylamine → {1-[2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-acetyl]-piperidin-4-yl}-carbamic acid butyl ester

HRID 1970629Notes

Reaction equation

HRID 1970629 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:68][C:69](=[O:81])[NH:70][CH:71]1[CH2:76][CH2:75][N:74]([C:77](=[O:80])[CH2:78][NH2:79])[CH2:73][CH2:72]1)[CH2:65][CH2:66][CH3:67]>CN(C=O)C>[CH2:64]([O:68][C:69](=[O:81])[NH:70][CH:71]1[CH2:72][CH2:73][N:74]([C:77](=[O:80])[CH2:78][NH:79][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])[CH2:75][CH2:76]1)[CH2:65][CH2:66][CH3:67]

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 668546955-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carboxylic acidHCID 66855388[1-(2-Amino-acetyl)-piperidin-4-yl]carbamic acid butyl ester

Product 1

HCID 66856251{1-[2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-acetyl]-piperidin-4-yl}-carbamic acid butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To solution of 250 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 231 mg HATU, 0.10 ml DIPEA and 156 mg [1-(2-Amino-acetyl)-piperidin-4-yl]-carbamic acid butyl ester. After stirring for 12 h it was concentrated and the residue dissolved in dichloromethane. It was extracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated to furnish the crude coupling product which was further 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. concentrationwas concentrated
  2. dissolutionthe residue dissolved in dichloromethane
  3. extractionIt was extracted with aqueous LiCl (4% w/w), aqueous NaHCO3 and 0.1 M HCl
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customto furnish the crude coupling product which
  7. customwas further purified by preparative HPLC (
  8. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-ae4a9100ce4b4cfa85a2190b54ec9f11
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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