Hydrochloric Acid → US10759813, Example 17-A

HRID 1052914Notes

Reaction equation

HRID 1052914 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[C@H:5]([OH:25])[CH2:6][C@H:7]([NH:16][C:17]([C:19]1[N:20]=[N:21][N:22]([OH:24])[CH:23]=1)=[O:18])[CH2:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[CH3:2].[Cl:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.C([O-])([O-])=O.[K+].[K+].Cl.O1CCOCC1>[Pd].O.CCO>[CH2:1]([O:3][C:4](=[O:26])[C@H:5]([OH:25])[CH2:6][C@H:7]([NH:16][C:17]([C:19]1[N:20]=[N:21][N:22]([OH:24])[CH:23]=1)=[O:18])[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:32]2[CH:31]=[CH:30][CH:29]=[C:28]([Cl:27])[CH:33]=2)=[CH:11][CH:10]=1)[CH3:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2734323(3-Chlorophenyl)boronic acidHCID 67969558(2R,4R)-5-(4-Bromophenyl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)amino]pentanoic Acid Ethyl Ester

Product 1

HCID 57378091US10759813, Example 17-A

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

(2R,4R)-5-(4-Bromo-phenyl)-2-hydroxy-4-[(1-hydroxy-1H-1,2,3-triazole-4-carbonyl)-amino]-pentanoic acid ethyl ester (120 mg, 281 μmol) and 3-chlorophenylboronic acid, pinacol ester (120 mg, 506 μmol) were combined with K2CO3 (116 mg, 842 μmol), EtOH (3 mL), and water (0.8 mL). SilicaCat®DPP-Pd (280 μmol/g loading; 1 mg, 28 μmol) was then added and the mixture was heated at 90° C. and the reaction monitored by LC/MS. The reaction was stopped after 2 hours, and the mixture was filtered, concentrated and purified (C18 reverse phase column; 30-70% MeCN in water with 0.05% TFA). EtOH (5.0 mL, 86 mmol) and 4 M HCl in dioxane (1.5 mL, 6.0 mmol) was added and the resulting mixture was stirred at room temperature for 40 minutes, then concentrated and purified (C18 reverse phase column; 30-90% MeCN in water with 0.05% TFA) to yield the title compound (20 mg; purity 95%). MS m/z [M+H]+ calc'd for C22H23ClN4O5, 459.14. found 459.4.

Workup

  1. filtrationthe mixture was filtered
  2. concentrationconcentrated
  3. custompurified (C18 reverse phase column; 30-70% MeCN in water with 0.05% TFA)
  4. concentrationconcentrated
  5. custompurified (C18 reverse phase column; 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-44fda75296c945ce93134518a732675e
Source dataset
uspto-grants-2016_07
Patent number
US09388145B2

Reaction notes

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