Hydrochloric Acid → Biphenyl-4-carboxylic acid (R)-(6-(1-((2-tert-butoxyethyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amide

HRID 2224744Notes

Reaction equation

HRID 2224744 reaction equation
I.[C:2]([O:6][CH2:7][CH2:8][N:9]([CH3:14])[CH:10](SC)[CH3:11])([CH3:5])([CH3:4])[CH3:3].Cl.C(OCCN)(C)(C)C.[NH2:24][C:25]1[CH:33]=[C:32]2[C:28]([CH2:29][C@@H:30]([OH:49])[C@@H:31]2[NH:34][C:35]([C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[CH:39][CH:38]=2)=[O:36])=[CH:27][CH:26]=1>N1C=CC=CC=1>[C:2]([O:6][CH2:7][CH2:8][N:9]([CH3:14])[C:10](=[N:24][C:25]1[CH:33]=[C:32]2[C:28]([CH2:29][C@@H:30]([OH:49])[C@@H:31]2[NH:34][C:35]([C:37]2[CH:42]=[CH:41][C:40]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)=[CH:39][CH:38]=2)=[O:36])=[CH:27][CH:26]=1)[CH3:11])([CH3:5])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24841Hydrogen iodideHCID 219146142-(Tert-butoxy)ethanamineHCID 44185809(R)-(4-biphenylcarbonylamino)-2(R)-hydroxy-6-aminoindaneHCID 86607042(2-Tert-butoxyethyl)methyl-(1-methylsulfanylethyl)amine

Product 1

HCID 58689453Biphenyl-4-carboxylic acid (R)-(6-(1-((2-tert-butoxyethyl)methylamino)ethylideneamino)-2(R)-hydroxyindan-1-yl)amideYield 22%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Dissolve the crude HI salt of (2-tert-butoxyethyl)methyl-(1-methylsulfanylethyl)amine (obtained using the crude HCl salt of 2-tert-butoxyethylamine, referenced in Example 9-1, using the methodology detailed in Example 6-1) (297.1 mg, 0.897 mmol) in 20 mL pyridine and add biphenyl-4-carboxylic acid (R)-(6-amino-2(R)-hydroxyindan-1-yl)amide (290.7 mg, 0.844 mmol). Allow the reaction to stir for 18 hours. Remove the solvent in vacuo and dissolve the residue in methylene chloride and wash with saturated aqueous sodium hydrogen carbonate. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to afford 248.7 mg of crude product. Purify the residue by Biotage chromatography (10% MeOH/EtOAc to 25% MeOH/EtOAc) to afford 91.7 mg of the titled product (22% yield). MS (ES): m/z 500.5 (M+H).

Workup

  1. customobtained
  2. customthe reaction
  3. customRemove the solvent in vacuo
  4. dissolutiondissolve the residue in methylene chloride
  5. washwash with saturated aqueous sodium hydrogen carbonate
  6. dry with materialDry the organic layer with magnesium sulfate
  7. filtrationFilter
  8. customremove the solvent in vacuo
  9. customto afford 248.7 mg of crude product
  10. customPurify the residue by Biotage chromatography (10% MeOH/EtOAc to 25% MeOH/EtOAc)

Sources & evidence

ORD record
ord-9e5c9b9d67914855a0914202de7e2192
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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