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

HRID 1970552Notes

Reaction equation

HRID 1970552 reaction equation
C([O:5][C:6](=[O:43])[CH2:7][CH2:8][C@H:9]([NH:13][C:14]([C:16]1[CH:20]=[C:19]([O:21][CH2:22][C:23]([N:25]2[CH2:29][CH2:28][CH2:27][C@H:26]2[C:30](=[O:36])[NH:31][CH:32]2[CH2:35][CH2:34][CH2:33]2)=[O:24])[N:18]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[N:17]=1)=[O:15])[C:10](O)=[O:11])(C)(C)C.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:77]1([O:83][C:84]([N:86]2[CH2:91][CH2:90][NH:89][CH2:88][CH2:87]2)=[O:85])[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=1>CN(C=O)C>[C:77]1([O:83][C:84]([N:86]2[CH2:91][CH2:90][N:89]([C:10](=[O:11])[C@@H:9]([NH:13][C:14]([C:16]3[CH:20]=[C:19]([O:21][CH2:22][C:23]([N:25]4[CH2:29][CH2:28][CH2:27][C@H:26]4[C:30](=[O:36])[NH:31][CH:32]4[CH2:33][CH2:34][CH2:35]4)=[O:24])[N:18]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:17]=3)=[O:15])[CH2:8][CH2:7][C:6]([OH:43])=[O:5])[CH2:88][CH2:87]2)=[O:85])[CH:82]=[CH:81][CH:80]=[CH:79][CH:78]=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 14896427Phenyl piperazine-1-carboxylateHCID 66854820(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanedioic acid 5-tert-butyl ester

Product 1

HCID 441293714-[(S)-4-Carboxy-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-butyryl]-piperazine-1-carboxylic acid phenyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 100 mg (S)-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanedioic acid 5-tert-butyl ester in 5 ml DMF were added 55 μl DIPEA, 64 mg HATU and 54 mg piperazine-1-carboxylic acid phenyl ester hydrotrifluoroacetate. After stirring for 36 h the solution was concentrated, the residue dissolved in 1.5 ml dichloromethane and treated with 190 μl TFA. After stirring for 4 h the solvents were removed under reduced pressure and the residue purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were lyophilized to yield the pure product. Yield: 40 mg MS (ES+): m/e=730.

Workup

  1. concentrationwas concentrated
  2. dissolutionthe residue dissolved in 1.5 ml dichloromethane
  3. additiontreated with 190 μl TFA
  4. stirringAfter stirring for 4 h the solvents
  5. customwere removed under reduced pressure
  6. customthe residue purified by preparative HPLC (
  7. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  8. additionThe fractions containing the product
  9. customto yield the pure product

Sources & evidence

ORD record
ord-18df614d5bec4bcd9975729b38a1ae1b
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

Loading…