1-Piperazinecarboxylic acid, ethyl ester → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-2-cyclohexyl-acetyl]-piperazine-1-carboxylic acid ethyl ester

HRID 1970620Notes

Reaction equation

HRID 1970620 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:40])[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]([NH:29][C@@H:30]([CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)[C:31](O)=[O:32])=[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.[CH2:74]([O:76][C:77]([N:79]1[CH2:84][CH2:83][NH:82][CH2:81][CH2:80]1)=[O:78])[CH3:75]>CN(C=O)C>[CH2:74]([O:76][C:77]([N:79]1[CH2:80][CH2:81][N:82]([C:31](=[O:32])[C@@H:30]([NH:29][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[CH2:2][CH2:3][CH2:4]3)=[O:40])[N:20]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:19]=2)=[O:28])[CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[CH2:83][CH2:84]1)=[O:78])[CH3:75]

Participants

6

Reactant 4

HCID 84311-Piperazinecarboxylic acid, ethyl esterHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66855107(S)-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-cyclohexyl-acetic acid

Product 1

HCID 668562064-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-2-cyclohexyl-acetyl]-piperazine-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 122 mg (S)-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-cyclohexyl-acetic acid in 2.5 ml DMF were added 84 mg HATU, 116 l DIPEA and 32 l 1-ethoxycarbonylpiperazine. After stirring for 12 h it was concentrated and the crude product thus obtained was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA) to give the title compound. Yield: 60 mg MS (ES+): m/e=692.

Workup

  1. concentrationwas concentrated
  2. customthe crude product thus obtained
  3. customwas purified by preparative HPLC (
  4. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)

Sources & evidence

ORD record
ord-cab09315f9814bf3bd5763533f3f4f41
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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