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

HRID 516468Notes

Reaction equation

HRID 516468 reaction equation
FC(F)(C(F)(F)F)C[O:4][C:5](=[O:26])[C@H:6]([OH:25])[CH2:7][C@H:8]([NH2:24])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=2[F:23])=[CH:12][CH:11]=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>>[Cl:22][C:20]1[CH:19]=[CH:18][C:17]([F:23])=[C:16]([C:13]2[CH:12]=[CH:11][C:10]([CH2:9][C@@H:8]([NH:24][C:38]([C:36]3[N:35]=[N:34][N:33]([OH:32])[CH:37]=3)=[O:39])[CH2:7][C@@H:6]([OH:25])[C:5]([OH:4])=[O:26])=[CH:15][CH:14]=2)[CH:21]=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 86705155HCID 86705155, compound

Product 1

HCID 67969390(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic AcidYield 16%

Procedure

(2R,4R)-4-Amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid 2,2,3,3,3-pentafluoropropyl ester (32.1 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 liquid, 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 (4.9 mg). MS m/z [M+H]+ calc'd for C23H19ClF6N4O5, 581.09. found 581.

Workup

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

Sources & evidence

ORD record
ord-7e6d168c16f642a390d10d88d0b79a0c
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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