Dimethylformamide → (2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid 5-Methyl-2-oxo-[1,3]dioxol-4-ylmethyl Ester

HRID 516448Notes

Reaction equation

HRID 516448 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:25][N:26]1[C:30]2[CH:31]=[C:32]([C:35]([OH:37])=O)[CH:33]=[CH:34][C:29]=2[N:28]=[N:27]1.CN(C=O)C.[CH3:43][C:44]1[O:48][C:47](=[O:49])[O:46][C:45]=1[CH2:50][O:51][C:52](=[O:72])[C@H:53]([OH:71])[CH2:54][C@H:55]([NH2:70])[CH2:56][C:57]1[CH:62]=[CH:61][C:60]([C:63]2[CH:68]=[CH:67][CH:66]=[C:65]([Cl:69])[CH:64]=2)=[CH:59][CH:58]=1.CCN(C(C)C)C(C)C>>[CH3:43][C:44]1[O:48][C:47](=[O:49])[O:46][C:45]=1[CH2:50][O:51][C:52](=[O:72])[C@H:53]([OH:71])[CH2:54][C@H:55]([NH:70][C:35]([C:32]1[CH:33]=[CH:34][C:29]2[N:28]=[N:27][N:26]([OH:25])[C:30]=2[CH:31]=1)=[O:37])[CH2:56][C:57]1[CH:62]=[CH:61][C:60]([C:63]2[CH:68]=[CH:67][CH:66]=[C:65]([Cl:69])[CH:64]=2)=[CH:59][CH:58]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 24237871-hydroxy-1H-1,2,3-benzotriazole-6-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86705143(2R,4R)-4-Amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo[1,3]dioxol-4-ylmethyl ester

Product 1

HCID 86705142(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid 5-Methyl-2-oxo-[1,3]dioxol-4-ylmethyl EsterYield 96%

Procedure

HATU (37.9 mg, 99.6 μmol) was added to a solution of 1-hydroxy-1H-1,2,3-benzotriazole-6-carboxylic acid (14.9 mg, 83 μmol) in DMF (0.5 mL, 6.4 mmol) and the resulting mixture was stirred at room temperature for 5 minutes. (2R,4R)-4-Amino-5-(3′-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo[1,3]dioxol-4-ylmethyl ester (28.7 mg, 66.4 μmol) was added to the mixture, followed by DIPEA (35 μL, 0.2 mmol) dropwise over 5 minutes, and the mixture was stirred at room temperature for 30 minutes. The mixture was concentrated in vacuo to yield a yellow liquid, which was purified by preparative HPLC to yield the title compound as a white solid (37.8 mg, purity 98.5%). MS m/z [M+H]+ calc'd for C29H25ClN4O8, 593.14. found 593.0.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. concentrationThe mixture was concentrated in vacuo
  3. customto yield a yellow liquid, which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-76b25f7e8baf4af58dfbc4fd04868e4a
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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