Hydrochloric Acid → HCID 57837464, compound

HRID 731751Notes

Reaction equation

HRID 731751 reaction equation
[CH:1]([C:4]1[C:12]([C:13](=[O:16])[CH2:14][CH3:15])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2].[CH2:17]=O.Cl.[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>CCOCC.[OH-].[Na+].CCOC(C)=O.CCCCCC>[CH2:20]([NH:27][CH2:15][CH:14]([CH3:17])[C:13]([C:12]1[C:4]([CH:1]([CH3:3])[CH3:2])=[N:5][N:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=12)=[O:16])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 2724127Benzylammonium chlorideHCID 10910951HCID 10910951, compound

Product 1

HCID 57837464HCID 57837464, compoundYield 9.5%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 14798Sodium HydroxideSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To 2-isopropyl-pyrazolo[1,5-a]pyridine (6.80 g, 42.50 mmol) in n-propionic anhydride (15 mL, 97%) at 140° C. was added concentrated H2SO4 (0.5 ml). The mixture was maintained at 140° C. overnight, cooled to room temperature basified with NaOH (aqueous 50%) until pH>11. The aqueous layer was extracted with chloroform (3×100 mL), dried (Na2SO4), filtered and concentrated. The crude product was purified by flash column chromatography (100% hexane, 9:1 hexane:ethyl acetate) to afford 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)propan-1-one (4.81 g, 22.27 mmol, 53%) as a yellow oil. 1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)propan-1-one (0.500 g, 2.3 mmol), paraformaldehyde (0.069 g, 2.3 mmol), and benzylamine hydrochloride (0.329 g, 2.3 mmol) were added to a 5-mL round bottom flask. To this ethanolic hydrochloride (1 mL, 1.25% concentrated HCl in ethanol) was added and the mixture was heated to reflux for 16 hours. The mixture was then cooled and diluted with Et2O (5 mL) and 1M NaOH (aq) (10 mL). The aqueous layer was then extracted with Et2O (4×5 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated to afford a dark brown oil. This oil was subjected to flash column chromatography (10% gradient of EtOAc/hexane ranging from 0 to 90%) which afforded 0.073 g (9.5% yield) of 3-(benzylamino)-1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one as a pale yellow oil.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 16 hours
  3. temperatureThe mixture was then cooled
  4. extractionThe aqueous layer was then extracted with Et2O (4×5 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a dark brown oil

Sources & evidence

ORD record
ord-d3d29c177cd5437f9ec155841b0a3a95
Source dataset
uspto-grants-2009_09
Patent number
US07585875B2

Reaction notes

Loading…