Hydrochloric Acid → HCID 178438693, compound

HRID 1688608Notes

Reaction equation

HRID 1688608 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]2[C:17](=[O:38])[N:18]([CH:28]3[CH2:31][CH:30]([C:32]([O:34]CCC)=O)[CH2:29]3)[C:19]3[N:20]([N:25]=[CH:26][N:27]=3)[C:21]=2[CH2:22][CH2:23][CH3:24])=[CH:11][CH:10]=1)#[N:2].[OH-].[Na+].Cl.[CH3:42][Mg]Br.[Cl-].[NH4+]>O1CCCC1.O.CO>[C:32]([C@H:30]1[CH2:31][C@H:28]([N:18]2[C:17](=[O:38])[C:16]([CH2:15][C:12]3[CH:13]=[CH:14][C:9]([C:4]4[C:3]([C:1]#[N:2])=[CH:8][CH:7]=[CH:6][CH:5]=4)=[CH:10][CH:11]=3)=[C:21]([CH2:22][CH2:23][CH3:24])[N:20]3[N:25]=[CH:26][N:27]=[C:19]23)[CH2:29]1)(=[O:34])[CH3:42]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 67009019propyl 3-{6-[(2'-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclobutanecarboxylateHCID 178418573HCID 178418573, compound

Product 1

HCID 178438693HCID 178438693, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of propyl 3-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}cyclobutanecarboxylate (5 g), 1N aqueous sodium hydroxide solution (10 mL), methanol (10 mL) and tetrahydrofuran (10 mL) was stirred at room temperature for 2 hr. The reaction mixture was adjusted to pH 4 with water and 1 N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained extract was dissolved in N,N-dimethylformamide (50 mL), N-methoxymethanamine hydrochloride (1.4 g), 1-hydroxybenzotriazole (2.3 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.8 g) and triethylamine (2.1 mL) were added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 N hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by purification by silica gel column chromatography was dissolved in tetrahydrofuran (20 mL), and methylmagnesium bromide (1.0 M tetrahydrofuran solution, 8.1 mL) was added at room temperature. The reaction mixture was stirred for 3 hr, saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (1.3 g, 28%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. extractionThe obtained extract
  6. dissolutionwas dissolved in N,N-dimethylformamide (50 mL)
  7. additionN-methoxymethanamine hydrochloride (1.4 g), 1-hydroxybenzotriazole (2.3 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.8 g) and triethylamine (2.1 mL) were added
  8. stirringthe mixture was stirred at room temperature for 16 hr
  9. additionThe reaction mixture was diluted with ethyl acetate
  10. washwashed with 1 N hydrochloric acid
  11. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customThe residue obtained by purification by silica gel column chromatography
  14. stirringThe reaction mixture was stirred for 3 hr
  15. extractionthe mixture was extracted with ethyl acetate
  16. washThe obtained ethyl acetate layer was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was evaporated under reduced pressure
  19. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-99e3c1d4334f459d8479a3195386dd89
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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