Hydrochloric Acid → HCID 52934333, compound

HRID 2366946Notes

Reaction equation

HRID 2366946 reaction equation
[H-].[Na+].[CH3:3][CH:4]([O:6][C:7](=[O:25])[NH:8][C@H:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]#[N:20])[CH:17]=2)[N:12]([C:21](=[O:23])[CH3:22])[C@@H:11]([CH3:24])[CH2:10]1)[CH3:5].CC(C)C=O.[NH2:31][CH2:32][CH:33]=O.Cl>CO.C(O)(=O)C>[CH3:5][CH:4]([O:6][C:7](=[O:25])[NH:8][C@H:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:19]3[NH:31][CH:32]=[CH:33][N:20]=3)[CH:17]=2)[N:12]([C:21](=[O:23])[CH3:22])[C@@H:11]([CH3:24])[CH2:10]1)[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 68185395HCID 68185395, compoundHCID 86669274HCID 86669274, compound

Product 1

HCID 52934333HCID 52934333, compoundYield 3.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

Sodium hydride (60% in mineral oil, 50 mg, 1.25 mmol) was added portionwise to a stirred solution of 1-methylethyl[(2S,4R)-1-acetyl-6-cyano-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 57) (350 mg, 1.1 mmol) in dry methanol (10 mL). The resulting mixture was stirred at room temperature for 48 h then was treated with aminoacetaldehyde dimethyl acetaldehyde (233 mg, 2.2 mmol) and acetic acid (1 mL, excess). The resulting mixture was refluxed for 2 h then was cooled to room temperature and treated with HCl (1M in water, 5 mL). The resulting mixture was refluxed for 1 h, cooled to room temperature and most of the methanol was removed in vacuo. The residue was diluted with water (10 mL) and basified by the addition of solid potassium carbonate (CARE: gas evolved). The resulting aqueous phase was extracted with AcOEt (3×10 mL). The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM) followed by trituration of the adduct obtained with Et2O gave 1-methylethyl[(2S,4R)-1-acetyl-6-(1H-imidazol-2-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (14 mg, 0.039 mmol, 3.5%) as an off white solid.

Workup

  1. temperatureThe resulting mixture was refluxed for 2 h
  2. temperaturethen was cooled to room temperature
  3. temperatureThe resulting mixture was refluxed for 1 h
  4. customwas removed in vacuo
  5. additionThe residue was diluted with water (10 mL)
  6. additionbasified by the addition of solid potassium carbonate (CARE: gas evolved)
  7. extractionThe resulting aqueous phase was extracted with AcOEt (3×10 mL)
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash chromatography on silica gel (gradient: 0 to 6% MeOH in DCM)
  12. customobtained with Et2O

Sources & evidence

ORD record
ord-1f41b7fa590d4aa7a951316bb1b342a5
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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