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 Butyryloxymethyl Ester

HRID 516474Notes

Reaction equation

HRID 516474 reaction equation
CCN(C(C)C)C(C)C.[C:10]([O:15][CH2:16][O:17][C:18](=[O:39])[C@H:19]([OH:38])[CH2:20][C@H:21]([NH2:37])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=2[F:36])=[CH:25][CH:24]=1)(=[O:14])[CH2:11][CH2:12][CH3:13].[OH:40][N:41]1[CH:45]=[C:44]([C:46](O)=[O:47])[N:43]=[N:42]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C=O)C>>[C:10]([O:15][CH2:16][O:17][C:18](=[O:39])[C@H:19]([OH:38])[CH2:20][C@H:21]([NH:37][C:46]([C:44]1[N:43]=[N:42][N:41]([OH:40])[CH:45]=1)=[O:47])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=2[F:36])=[CH:25][CH:24]=1)(=[O:14])[CH2:11][CH2:12][CH3:13]

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 86705163(2R,4R)-4-amino-5-(5'-chloro-2'-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester

Product 1

HCID 86705162(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid Butyryloxymethyl EsterYield 23.9%

Procedure

DIPEA (35.8 μL, 206 μmol) was added to a solution of (2R,4R)-4-amino-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxypentanoic acid butyryloxymethyl ester (30.0 mg, 68.5 μmol), 1-hydroxy-1H-1,2,3-triazole-4-carboxylic acid (13.3 mg, 103 μmol) and HATU (39.1 mg, 103 μmol) in DMF (500 μL, 6.5 mmol). The resulting mixture was stirred at room temperature for 30 minutes, then concentrated in vacuo to yield a clear yellow liquid. The crude liquid was purified by preparative scale HPLC (C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (9.0 mg). MS m/z [M+H]+ calc'd for C25H26ClFN4O7, 549.15. found 549.1.

Workup

  1. concentrationconcentrated in vacuo
  2. customto yield a clear yellow liquid
  3. customThe crude liquid was purified by preparative scale HPLC (C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-44006ff8e85b43698672963b6e09ef18
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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