Triethylamine → 3'-({2-[(4,4-Dimethylcyclohexyl)amino]ethyl}oxy)-4-biphenylcarboxamide hydrochloride

HRID 70339Notes

Reaction equation

HRID 70339 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([NH2:19])=[O:18])=[CH:13][CH:12]=2)[CH:8]=[CH:9][CH:10]=1.BrCCOC1C=C(C2C=CC(C(N)=O)=CC=2)C=CC=1.Cl.[CH3:40][C:41]1([CH3:48])[CH2:46][CH2:45][CH:44]([NH2:47])[CH2:43][CH2:42]1.C(N(CC)CC)C>CO.C(OCC)(=O)C>[ClH:1].[CH3:40][C:41]1([CH3:48])[CH2:46][CH2:45][CH:44]([NH:47][CH2:2][CH2:3][O:4][C:5]2[CH:6]=[C:7]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([NH2:19])=[O:18])=[CH:13][CH:12]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:43][CH2:42]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 241919284,4-Dimethylcyclohexanamine hydrochlorideHCID 582762623'-[(2-Bromoethyl)oxy]-4-biphenylcarboxamideHCID 582763523'-[(2-Chloroethyl)oxy]-4-biphenylcarboxamide

Product 1

HCID 671604303'-({2-[(4,4-Dimethylcyclohexyl)amino]ethyl}oxy)-4-biphenylcarboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3′-[(2-chloroethyl)oxy]-4-biphenylcarboxamide and 3′-[(2-bromoethyl)oxy]-4-biphenylcarboxamide (Example II-1) (0.15 g), 4,4-dimethylcyclohexylamine hydrochloride (0.13 g, 0.8 mmol) (prepared according to J. Med. Chem. 1971, 14, p. 600-614) and triethylamine (0.14 g, 1.35 mmol) in methanol (2 mL) was placed in a microwave at 160° C. until the reaction was complete as monitored by LC/MS. The reaction mixture was poured into ethyl acetate and washed several times with 5% Na2CO3 (aq). Silica gel was added to the organic phase and the mixture was concentrated in vacuo. The residue was purified by silica gel chromatography. The fractions containing the desired product were combined and concentrated in vacuo. Dissolved the residue in ethanol, added 1.0N HCl in Et2O until acidic, added ethyl ether until turbid and let stand at room temperature. The resulting solid was filtered, washed with ethyl ether and dried to give 3′-({2-[(4,4-dimethylcyclohexyl)amino]ethyl}oxy)-4-biphenylcarboxamide hydrochloride as an off-white solid. (M+H) 367, 1.83 min. (LC/MS method A)

Workup

  1. customwas placed in a microwave at 160° C. until the reaction
  2. washwashed several times with 5% Na2CO3 (aq)
  3. additionSilica gel was added to the organic phase
  4. concentrationthe mixture was concentrated in vacuo
  5. customThe residue was purified by silica gel chromatography
  6. additionThe fractions containing the desired product
  7. concentrationconcentrated in vacuo
  8. dissolutionDissolved the residue in ethanol
  9. additionadded 1.0N HCl in Et2O until acidic,
  10. additionadded ethyl ether until turbid
  11. customlet stand at room temperature
  12. filtrationThe resulting solid was filtered
  13. washwashed with ethyl ether
  14. customdried

Sources & evidence

ORD record
ord-31192e4280154abaa3955ea51a10d8f0
Source dataset
uspto-grants-2014_09
Patent number
US08822518B2

Reaction notes

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