Diisopropylethylamine → (2R,3R)-4-(2-Chlorophenyl)-2-hydroxy-3-[4-(3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl)-benzoylamino]-butyric acid ethyl ester

HRID 2361120Notes

Reaction equation

HRID 2361120 reaction equation
[CH3:1][C:2]1[CH2:6][C:5](=[O:7])[N:4]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:41]([O:43][C:44](=[O:57])[C@H:45]([OH:56])[C@H:46]([NH2:55])[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[Cl:54])[CH3:42].CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:41]([O:43][C:44](=[O:57])[C@H:45]([OH:56])[C@H:46]([NH:55][C:12](=[O:14])[C:11]1[CH:10]=[CH:9][C:8]([N:4]2[C:5](=[O:7])[CH2:6][C:2]([CH3:1])=[N:3]2)=[CH:16][CH:15]=1)[CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][C:49]=1[Cl:54])[CH3:42]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1090294-(3-Methyl-5-oxo-2-pyrazolin-1-yl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71073615(2R,3R)-3-Amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid ethyl ester

Product 1

HCID 71073793(2R,3R)-4-(2-Chlorophenyl)-2-hydroxy-3-[4-(3-methyl-5-oxo-4,5-dihydro-pyrazol-1-yl)-benzoylamino]-butyric acid ethyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

4-(3-Methyl-5-oxo-2-pyrazolin-1-yl)benzoic acid (100 mg, 0.6 mmol, 1.0 eq.) was combined with DMF (1000 μL) and HATU (250 mg, 0.7 mmol, 1.2 eq.) and stirred at room temperature for 15 minutes. (2R,3R)-3-Amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid ethyl ester (TFA salt, 200 mg, 0.6 mmol, 1.0 eq.) in DIPEA (200 μL, 2.0 eq.) and DMF (1000 μL) was then added and the resulting mixture was stirred overnight at room temperature. Excess solvent was removed and the product was dissolved in AcOH/H2O (50%) and purified by preparative LC (1″ column; gradient 2-50% MeCN/H2O, 0.05% TFA, over 80 minutes; 15 mL/min flow; UV 280 nm). The fractions were collected, frozen, and lyophilized to yield the title compound (100 mg, 98% purity). MS m/z [M+H]+ calc'd for C23H24ClN3O5, 458.14. found 458.2.

Workup

  1. stirringthe resulting mixture was stirred overnight at room temperature
  2. customExcess solvent was removed
  3. dissolutionthe product was dissolved in AcOH/H2O (50%)
  4. custompurified by preparative LC (1″ column
  5. waitgradient 2-50% MeCN/H2O, 0.05% TFA, over 80 minutes
  6. customThe fractions were collected
  7. temperaturefrozen

Sources & evidence

ORD record
ord-3801449a6aed4855ad33056638d6dc44
Source dataset
uspto-grants-2014_04
Patent number
US08686184B2

Reaction notes

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