Acetone → (2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-{[1-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethoxy)-1H-[1,2,3]triazole-4-carbonyl]amino}pentanoic Acid

HRID 516470Notes

Reaction equation

HRID 516470 reaction equation
Cl[CH2:2][C:3]1[O:4][C:5](=[O:9])[O:6][C:7]=1[CH3:8].[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([F:40])=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][C@@H:24]([NH:31][C:32]([C:34]3[N:35]=[N:36][N:37]([OH:39])[CH:38]=3)=[O:33])[CH2:25][C@@H:26]([OH:30])[C:27]([OH:29])=[O:28])=[CH:19][CH:18]=2)[CH:16]=1.CC(C)=O.CCN(CC)CC>>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([F:40])=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([CH2:23][C@@H:24]([NH:31][C:32]([C:34]3[N:35]=[N:36][N:37]([O:39][CH2:2][C:3]4[O:4][C:5](=[O:9])[O:6][C:7]=4[CH3:8])[CH:38]=3)=[O:33])[CH2:25][C@@H:26]([OH:30])[C:27]([OH:29])=[O:28])=[CH:19][CH:18]=2)[CH:16]=1

Participants

5

Reactant 4

HCID 180AcetoneHCID 8471TriethylamineHCID 98555184-(Chloromethyl)-5-methyl-1,3-dioxol-2-oneHCID 67969390(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-[1,2,3]triazole-4-carbonyl)amino]pentanoic Acid

Product 1

HCID 86705158(2R,4R)-5-(5'-Chloro-2'-fluorobiphenyl-4-yl)-2-hydroxy-4-{[1-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethoxy)-1H-[1,2,3]triazole-4-carbonyl]amino}pentanoic AcidYield 17.3%

Conditions

Temperature
65 °C

Procedure

4-Chloromethyl-5-methyl-1,3-dioxol-2-one (11.0 μL, 100 μmol) was added to a solution of (2R,4R)-5-(5′-chloro-2′-fluorobiphenyl-4-yl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)amino]pentanoic acid (30.0 mg, 66.8 μmol) in acetone (0.5 mL, 6.8 mmol). Et3N (18.6 μL, 134 μmol) was added and the resulting mixture was stirred at 65° C. for 2 hours. The mixture was concentrated in vacuo to yield a yellow solid. The crude solid 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 (6.5 mg). MS m/z [M+H]+ calc'd for C25H22ClFN4O5, 561.11. found 561.1.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto yield a yellow solid
  3. customThe crude solid 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-0644aae6a82c47438270830838692887
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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