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

HRID 516447Notes

Reaction equation

HRID 516447 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.[F:43][C:44]([F:72])([C:68]([F:71])([F:70])[F:69])[CH2:45][O:46][C:47](=[O:67])[C@H:48]([OH:66])[CH2:49][C@H:50]([NH2:65])[CH2:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([Cl:64])[CH:59]=2)=[CH:54][CH:53]=1.CCN(C(C)C)C(C)C>>[F:72][C:44]([F:43])([C:68]([F:69])([F:70])[F:71])[CH2:45][O:46][C:47](=[O:67])[C@H:48]([OH:66])[CH2:49][C@H:50]([NH:65][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])[CH2:51][C:52]1[CH:57]=[CH:56][C:55]([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([Cl:64])[CH:59]=2)=[CH:54][CH:53]=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 86705141(2R,4R)-4-Amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid 2,2,3,3,3-pentafluoropropyl ester

Product 1

HCID 72700395(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid 2,2,3,3,3-Pentafluoropropyl EsterYield 7.1%

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 2,2,3,3,3-pentafluoropropyl ester (30.0 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 (2.9 mg, purity 100%). MS m/z [M+H]+ calc'd for C27H22ClF5N4O5, 613.12. found 613.0.

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-bcc5b281e8334c75a5209c317385866f
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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