2-Pyridineacetic acid, hydrochloride (1:1) → n-[2-((s)-2-Imidazol-1-yl-1-phenyl-ethoxy)-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yl]-2-pyridin-2-yl-acetamide

HRID 496410Notes

Reaction equation

HRID 496410 reaction equation
[NH2:1][C:2]1[C:11]([O:12][C@@H:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:14][N:15]2[CH:19]=[CH:18][N:17]=[CH:16]2)=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][C:7]2=[O:26].Cl.[N:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[CH2:34][C:35](O)=[O:36].CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[N:15]1([CH2:14][C@H:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[O:12][C:11]2[CH:10]=[CH:9][C:8]3[C:7](=[O:26])[CH2:6][CH2:5][CH2:4][C:3]=3[C:2]=2[NH:1][C:35](=[O:36])[CH2:34][C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][N:28]=2)[CH:19]=[CH:18][N:17]=[CH:16]1

Participants

5

Reactant 3

HCID 853172-Pyridineacetic acid, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 600298675-Amino-6-((S)-2-imidazol-1-yl-1-phenyl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one

Product 1

HCID 60029945n-[2-((s)-2-Imidazol-1-yl-1-phenyl-ethoxy)-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yl]-2-pyridin-2-yl-acetamideYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-amino-6-((S)-2-imidazol-1-yl-1-phenyl-ethoxy)-3,4-dihydro-2H-naphthalen-1-one (100 mg, 0.288 mmol) and 2-pyridylacetic acid HCl (67 mg, 0.386 mmol) in DMF (3 mL) was added EDCI HCl (111 mg, 0.576 mmol, 2 equiv). The yellow solution turned orange overnight. Some of the DMF was removed under reduced pressure. The residue was dissolved in H2O and 1 M NaOH was added until the solution was basic (pH 10). The mixture was extracted thoroughly with CH2Cl2. The organic layer was washed with brine, dried over Na2SO4 and concentrated to give a bright yellow oil. Purification by chromatography (7% MeOH/CH2Cl2) afforded the title compound as a pale yellow foam (107 mg, 0.229 mmol, 80%). The structure was confirmed by NMR and mass spectrometry. MS m/z 467 (M++H).

Workup

  1. customSome of the DMF was removed under reduced pressure
  2. dissolutionThe residue was dissolved in H2O
  3. addition1 M NaOH was added until the solution
  4. extractionThe mixture was extracted thoroughly with CH2Cl2
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give a bright yellow oil
  9. customPurification by chromatography (7% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-9b87575430d64ae0a0817163efc730de
Source dataset
uspto-grants-2005_09
Patent number
US06943183B2

Reaction notes

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