Triethylamine → Biphenyl-4-carboxylic acid (R)-(6-(1-((2-methoxyethyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide

HRID 2224738Notes

Reaction equation

HRID 2224738 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH3:20])[C:6](=[N:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][C@@H:14]([OH:19])[C@@H:15]2[NH-:18])=[CH:11][CH:10]=1)[CH3:7].C(OC(=O)N)(C)(C)C.C(N(CC)CC)C.O=C1CCC(=O)N1[O:43][C:44]([C:46]1[CH:51]=[CH:50][C:49]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[CH:48][CH:47]=1)=O>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][N:5]([CH3:20])[C:6](=[N:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][C@@H:14]([OH:19])[C@@H:15]2[NH:18][C:44]([C:46]2[CH:51]=[CH:50][C:49]([C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=3)=[CH:48][CH:47]=2)=[O:43])=[CH:11][CH:10]=1)[CH3:7]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 6847362,5-Dioxopyrrolidin-1-yl [1,1'-biphenyl]-4-carboxylateHCID 86607037carbamic acid tert-butyl ester (R)-(6-(1-((2-methoxyethyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide

Product 1

HCID 9804160Biphenyl-4-carboxylic acid (R)-(6-(1-((2-methoxyethyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amideYield 50.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

Dissolve carbamic acid tert-butyl ester (R)-(6-(1-((2-methoxyethyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide (153.6 mg, 0.407 mmol) in excess TFA at 0° C. and allow to stir for 1 hour. Remove the solvent in vacuo. Dissolve the residue in 10 mL methylene chloride and add triethylamine (411.8 mg, 4.07 mmol) and biphenyl-4-carboxylic acid 2,5-dioxopyrrolidin-1-yl ester (118.3 mg, 0.400 mmol). Allow the reaction mixture to stir for 21 hours. Dilute the reaction mixture with methylene chloride and wash it with saturated aqueous sodium hydrogen carbonate (1×) and brine (1×). Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to give 162.1 mg of crude product. Purify via Biotage chromatography (30% MeOH/EtOAc) to afford 93.1 mg of the titled product as an oil (50% yield). MS (ES): m/z 458.3(M+H).

Workup

  1. customRemove the solvent in vacuo
  2. dissolutionDissolve the residue in 10 mL methylene chloride
  3. stirringto stir for 21 hours
  4. washwash it with saturated aqueous sodium hydrogen carbonate (1×) and brine (1×)
  5. dry with materialDry the organic layer with magnesium sulfate
  6. filtrationFilter
  7. customremove the solvent in vacuo
  8. customto give 162.1 mg of crude product
  9. customPurify via Biotage chromatography (30% MeOH/EtOAc)

Sources & evidence

ORD record
ord-593ec59d33854cd781be148627bb5bca
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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