Diisopropylethylamine → (S)-5-(3-Butoxycarbonylamino-pyrrolidin-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 1970479Notes

Reaction equation

HRID 1970479 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.[CH2:77]([O:81][C:82](=[O:89])[NH:83][CH:84]1[CH2:88][CH2:87][NH:86][CH2:85]1)[CH2:78][CH2:79][CH3:80]>CN(C=O)C.C(OCC)(=O)C>[CH2:77]([O:81][C:82]([NH:83][CH:84]1[CH2:88][CH2:87][N:86]([C:10](=[O:11])[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:38]=[CH:39][CH:40]=[CH:41][CH:42]=3)[N:17]=2)=[O:15])[CH2:8][CH2:7][C:6]([OH:43])=[O:5])[CH2:85]1)=[O:89])[CH2:78][CH2:79][CH3:80]

Participants

7

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 20242877Pyrrolidin-3-yl-carbamic acid butyl esterHCID 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 44128983(S)-5-(3-Butoxycarbonylamino-pyrrolidin-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 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 303 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 34 μl DIPEA, 193 mg HATU and 103 mg pyrrolidin-3-yl-carbamic acid butyl ester. After stirring for 12 h the reaction mixture was diluted with ethyl acetate, washed with aqueous LiCl (4%) and saturated aqueous NaHCO3 solution. The solution was concentrated, dissolved in 2 ml dichloromethane and stirred in the presence of 384 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: 229 mg MS (ES+): m/e=710.

Workup

  1. washwashed with aqueous LiCl (4%) and saturated aqueous NaHCO3 solution
  2. concentrationThe solution was concentrated
  3. dissolutiondissolved in 2 ml dichloromethane
  4. stirringstirred in the presence of 384 μl TFA
  5. stirringAfter stirring for 4 h the solvents
  6. customwere removed under reduced pressure
  7. customthe residue purified by preparative HPLC (
  8. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  9. additionThe fractions containing the product
  10. customto yield the pure product

Sources & evidence

ORD record
ord-d353667185244166a88f51bbdfeeb4e6
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

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