Diisopropylethylamine → (S)-5-[4-(3-Chloro-benzoyl)-piperidin-1-yl]-4-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-oxo-pentanoic acid

HRID 1970469Notes

Reaction equation

HRID 1970469 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]([OH:12])=O)(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.[Cl:77][C:78]1[CH:79]=[C:80]([CH:89]=[CH:90][CH:91]=1)[C:81]([CH:83]1[CH2:88][CH2:87][NH:86][CH2:85][CH2:84]1)=[O:82].C([O-])(O)=O.[Na+]>CN(C=O)C>[Cl:77][C:78]1[CH:79]=[C:80]([CH:89]=[CH:90][CH:91]=1)[C:81]([CH:83]1[CH2:84][CH2:85][N:86]([C:10](=[O:12])[C@@H:9]([NH:13][C:14]([C:16]2[CH:20]=[C:19]([O:21][CH2:22][C:23]([N:25]3[CH2:29][CH2:28][CH2:27][C@H:26]3[C:30](=[O:36])[NH:31][CH:32]3[CH2:33][CH2:34][CH2:35]3)=[O:24])[N:18]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:17]=2)=[O:15])[CH2:8][CH2:7][C:6]([OH:5])=[O:43])[CH2:87][CH2:88]1)=[O:82]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 3645096(3-Chlorophenyl)(piperidin-4-yl)methanoneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 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 66855093(S)-5-[4-(3-Chloro-benzoyl)-piperidin-1-yl]-4-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-oxo-pentanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 150 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 7 ml DMF were added 62 μl DIPEA, 95 mg HATU and 56 mg 4-(3-chlorobenzoyl)-piperidine. After stirring for 12 h saturated NaHCO3 solution was added and the mixture loaded on a Chem Elut® cartridge, the crude product being eluted with dichloromethane. The solution was concentrated to a volume of 1 ml and stirred in the presence of 100 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: 135 mg MS (ES+): m/e=747.

Workup

  1. additionwas added
  2. washthe crude product being eluted with dichloromethane
  3. concentrationThe solution was concentrated to a volume of 1 ml
  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-f82cf5bb22404066a25b5e76968af9d9
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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