Dimethylformamide → (2R,3R)-3-(1-((2'-(N-Acetylsulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-2-hydroxy-4-phenylbutanoic Acid

HRID 71658Notes

Reaction equation

HRID 71658 reaction equation
[C:1]([NH:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:25]([CH2:26][CH2:27][CH3:28])=[CH:24][C:23](C(O)=O)=[N:22]2)=[CH:16][CH:15]=1)(=[O:7])=[O:6])(=[O:3])[CH3:2].CN([C:35]([O:39]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN(C=O)C.[NH2:70][C@H:71]([CH2:77][C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)[C@@H:72]([OH:76])[C:73]([OH:75])=[O:74]>>[C:1]([NH:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:25]([CH2:26][CH2:27][CH3:28])=[CH:24][C:23]([C:35]([NH:70][C@H:71]([CH2:77][C:78]3[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=3)[C@@H:72]([OH:76])[C:73]([OH:75])=[O:74])=[O:39])=[N:22]2)=[CH:16][CH:15]=1)(=[O:6])=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 638739(2R,3R)-3-amino-2-hydroxy-4-phenylbutanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 667576391-(2'-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid

Product 1

HCID 66757852(2R,3R)-3-(1-((2'-(N-Acetylsulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-2-hydroxy-4-phenylbutanoic AcidYield 97%

Conditions

Temperature
45 °C

Procedure

A solution of 1-(2′-acetylsulfamoylbiphenyl-4-ylmethyl)-5-propyl-1H-pyrazole-3-carboxylic acid (250 mg, 570 μmol), HATU (215 mg, 566 μmol) and DIPEA (592 μL, 3.4 mmol) in DMF (18 mL, 230 mmol) was stirred to pre-activate the acid. After 15 minutes, (2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid (110 mg, 566 μmol) was added. The resulting solution was stirred at 45° C. overnight. The mixture was concentrated, re-dissolved in water/MeCN/TFA and purified using reverse phase liquid chromatography to yield the title compound (197 mg, 97% purity). MS m/z: [M+H]+ calcd for C32H34N4O7S, 619.22. found 619.6.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionre-dissolved in water/MeCN/TFA
  3. custompurified

Sources & evidence

ORD record
ord-37dbbb980e384507b150930d32e3f1f8
Source dataset
uspto-grants-2014_09
Patent number
US08822522B2

Reaction notes

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