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

HRID 1643996
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Reaktionsgleichung

Reaktionsgleichung von HRID 1643996
[CH3:1][O:2][C:3]([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:15]1[CH:20]=[CH:19][C:18]([CH2:21][N:22]2[C:26]([CH2:27][CH2:28][CH3:29])=[CH:25][C:24]([C:30]([OH:32])=O)=[N:23]2)=[CH:17][CH:16]=1)(=[O:8])=[O:7])=[O:4].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.CN(C=O)C.[NH2:71][C@H:72]([CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)[C@@H:73]([OH:77])[C:74]([OH:76])=[O:75]>>[OH:77][C@H:73]([C@H:72]([NH:71][C:30]([C:24]1[CH:25]=[C:26]([CH2:27][CH2:28][CH3:29])[N:22]([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[S:6](=[O:8])(=[O:7])[NH:5][C:3]([O:2][CH3:1])=[O:4])=[CH:16][CH:17]=2)[N:23]=1)=[O:32])[CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)[C:74]([OH:76])=[O:75]
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Komponenten

6

Edukt 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 581029031-((2'-(N-(methoxycarbonyl)sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxylic acid

Produkt 1

HCID 58102914(2R,3R)-2-hydroxy-3-(1-((2'-(N-(methoxycarbonyl)-sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxamido)-4-phenylbutanoic AcidAusbeute 95 %

Versuchsvorschrift

A solution of 1-((2′-(N-(methoxycarbonyl)sulfamoyl)biphenyl-4-yl)methyl)-5-propyl-1H-pyrazole-3-carboxylic acid (40.2 mg, 87.8 μmol), DIPEA (91.8 μL, 527 μmol) and HATU (33.4 mg, 87.8 μmol) in DMF (0.4 mL, 4 mmol) was stirred to pre-activate the acid. After 1 minute, (2R,3R)-3-amino-2-hydroxy-4-phenylbutyric acid (17.1 mg, 87.8 μmol) was added, and the mixture was stirred for 10 minutes. The reaction was quenched by adding 1 N HCl and extracted with DCM. The organic layer was added to AcOH (1 mL) and evaporated in vacuo. The material was then purified by preparative HPLC to yield the title compound (10 mg, 95% purity). MS m/z: [M+H]+ calcd for C32H34N4O8S, 635.21; found 635.20.

Aufarbeitung

  1. customThe reaction was quenched
  2. additionby adding 1 N HCl
  3. extractionextracted with DCM
  4. additionThe organic layer was added to AcOH (1 mL)
  5. customevaporated in vacuo
  6. customThe material was then purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-26474ebbdecc442e837b7b0e42adb08b
Quelldatensatz
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08119634B2

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