Acetone → HCID 86705160, compound

HRID 516472Notes

Reaction equation

HRID 516472 reaction equation
Cl[CH2:2][O:3][C:4](=[O:17])[C@@H:5]([NH:9]C(OC(C)(C)C)=O)[CH:6]([CH3:8])[CH3:7].[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([F:48])=[C:23]([C:25]2[CH:30]=[CH:29][C:28]([CH2:31][C@@H:32]([NH:39][C:40]([C:42]3[N:43]=[N:44][N:45]([OH:47])[CH:46]=3)=[O:41])[CH2:33][C@@H:34]([OH:38])[C:35]([OH:37])=[O:36])=[CH:27][CH:26]=2)[CH:24]=1.CC(C)=O.CCN(CC)CC.C(O)(C(F)(F)F)=O.C(Cl)Cl>>[NH2:9][C@@H:5]([CH:6]([CH3:7])[CH3:8])[C:4]([O:3][CH2:2][O:47][N:45]1[CH:46]=[C:42]([C:40]([NH:39][C@H:32]([CH2:31][C:28]2[CH:29]=[CH:30][C:25]([C:23]3[CH:24]=[C:19]([Cl:18])[CH:20]=[CH:21][C:22]=3[F:48])=[CH:26][CH:27]=2)[CH2:33][C@@H:34]([OH:38])[C:35]([OH:37])=[O:36])=[O:41])[N:43]=[N:44]1)=[O:17]

Participants

6

Reactant 5

HCID 180AcetoneHCID 8471TriethylamineHCID 21863450Trifluoroacetic acid methylene chlorideHCID 54112037chloromethyl (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoateHCID 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 86705160HCID 86705160, compoundYield 10.4%

Conditions

Temperature
65 °C

Procedure

(S)-2-t-Butoxycarbonylamino-3-methylbutyric acid chloromethyl ester (44.4 mg, 167 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 mol) 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. 1:1 TFA/DCM (1.0 mL, 6.2 mmol) was added and the mixture was stirred at room temperature for 30 minutes, and then concentrated in vacuo to yield a yellow liquid. The crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA) to yield the title compound as a white solid (10 mg). MS m/z [M+H]+ calc'd for C26H29ClFN5O7, 578.17. found 578.1.

Workup

  1. stirringthe mixture was stirred at room temperature for 30 minutes
  2. concentrationconcentrated in vacuo
  3. customto yield a yellow liquid
  4. customThe crude liquid was purified (preparative scale C18 column chromatography, small column, using 30-90% MeCN in water with 0.05% TFA)

Sources & evidence

ORD record
ord-b689073fcfa042198e51c870fd866f37
Source dataset
uspto-grants-2015_08
Patent number
US09108934B2

Reaction notes

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