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

HRID 516469Notes

Reaction equation

HRID 516469 reaction equation
[CH3:1][C:2]1[O:6][C:5](=[O:7])[O:4][C:3]=1[CH2:8][O:9][C:10](=[O:31])[C@H:11]([OH:30])[CH2:12][C@H:13]([NH2:29])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=2[F:28])=[CH:17][CH:16]=1.[OH:32][N:33]1[CH:37]=[C:36]([C:38](O)=[O:39])[N:35]=[N:34]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C.CCN(C(C)C)C(C)C>>[CH3:1][C:2]1[O:6][C:5](=[O:7])[O:4][C:3]=1[CH2:8][O:9][C:10](=[O:31])[C@H:11]([OH:30])[CH2:12][C@H:13]([NH:29][C:38]([C:36]1[N:35]=[N:34][N:33]([OH:32])[CH:37]=1)=[O:39])[CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=2[F:28])=[CH:19][CH:20]=1

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 534331041-Hydroxy-1H-1,2,3-triazole-4-carboxylic AcidHCID 86705157(2R,4R)-4-Amino-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester

Product 1

HCID 86705156(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid 5-Methyl-2-oxo-[1,3]dioxol-4-ylmethyl EsterYield 70.7%

Procedure

(2R,4R)-4-Amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester (30.7 mg, 68.3 μmol), 1-hydroxy-1H-[1,2,3]triazole-4-carboxylic acid (10.6 mg, 82 μmol) and HATU (39.0 mg, 102 μmol) were stirred in DMF (1.0 mL, 12.9 mmol) for 10 minutes. DIPEA (35.7 μL, 205 μmol) was added dropwise and the resulting mixture was stirred at room temperature for 1 hour. The mixture was concentrated and to yield a clear yellow liquids, which was purified using preparative scale C18 column chromatography (small column; 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (27.1 mg). MS m/z [M+H]+ calc'd for C25H22ClFN4O8, 561.11. found 561.1.

Workup

  1. concentrationThe mixture was concentrated
  2. customto yield a clear yellow liquids, which
  3. customwas purified

Sources & evidence

ORD record
ord-e3f0259076b343e08065e18abd8b6231
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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