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

HRID 516449Notes

Reaction equation

HRID 516449 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.[C:43]([O:48][CH2:49][O:50][C:51](=[O:71])[C@H:52]([OH:70])[CH2:53][C@H:54]([NH2:69])[CH2:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([Cl:68])[CH:63]=2)=[CH:58][CH:57]=1)(=[O:47])[CH2:44][CH2:45][CH3:46].CCN(C(C)C)C(C)C>>[C:43]([O:48][CH2:49][O:50][C:51](=[O:71])[C@H:52]([OH:70])[CH2:53][C@H:54]([NH:69][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])[CH2:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]2[CH:67]=[CH:66][CH:65]=[C:64]([Cl:68])[CH:63]=2)=[CH:58][CH:57]=1)(=[O:47])[CH2:44][CH2:45][CH3:46]

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 86705144(2R,4R)-4-Amino-5-(3'-chlorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester

Product 1

HCID 72700647(2R,4R)-5-(3'-Chlorobiphenyl-4-yl)-2-hydroxy-4-[(3-hydroxy-3H-benzotriazole-5-carbonyl)amino]pentanoic Acid Butyryloxymethyl EsterYield 10.8%

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 butyryloxymethyl ester (27.9 mg, 66.4 mol) 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 (5.2 mg, purity 98.2%). MS m/z [M+H]+ calc'd for C29H29ClN4O7, 581.17. found 581.2.

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-5d55b90cc907456485ef2bc16a57366b
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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