Diethyl Ether → {8-[4-(1-Aminocyclopropyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-3-yl}methanol

HRID 1678780Notes

Reaction equation

HRID 1678780 reaction equation
[CH2:1]([Mg]Br)[CH3:2].C(OCC)C.[OH:10][CH2:11][C:12]1[N:24]2[C:15]([C:16]3[CH:17]=[C:18]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[C:19]([C:25]4[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[CH:27][CH:26]=4)=[N:20][C:21]=3[CH:22]=[CH:23]2)=[N:14][N:13]=1.B(F)(F)F.CCOCC>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH2:30][C:29]1([C:28]2[CH:31]=[CH:32][C:25]([C:19]3[C:18]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[CH:17][C:16]4[C:15]5=[N:14][N:13]=[C:12]([CH2:11][OH:10])[N:24]5[CH:23]=[CH:22][C:21]=4[N:20]=3)=[CH:26][CH:27]=2)[CH2:2][CH2:1]1

Participants

7

Reactant 4

HCID 3283Diethyl Ether2×HCID 8000Boron trifluoride etherateHCID 594729444-[3-(Hydroxymethyl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]benzonitrileHCID 178418443HCID 178418443, compound2×

Product 1

HCID 15979530{8-[4-(1-Aminocyclopropyl)phenyl]-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-3-yl}methanol

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Ethylmagnesium bromide in diethyl ether (0.4 mL, 1.2 mMol, 3M) was added at −70° C. to a solution of 15-1 (0.1 g, 0.3 mmol) and titanium (IV) isopropoxide (0.17 g, 0.6 mMol) in anhydrous THF (7 mL). After 10 min, the cold bath was removed and the reaction was warmed to room temperature. After stirring for 1 hour, more ethylmagnesium bromide in diethyl ether (0.18 mL, 0.5 mMol, 3M) was added and the reaction was cooled to 0° C. in an ice bath and was treated with boron trifluoride etherate (0.18 g, 1.2 mMol). The reaction was stirred at 0° C. for 30 minutes then warmed to room temperature for 1 hour. The reaction was quenched with 1N HCl followed by stirring for 3 hours. The solution was basified with 1M NaOH, extracted with chloroform, dried with Na2SO4, filtered and concentrated in vacuo. Crude residue was taken up in methanol and purified using a C18 reverse phase HPLC to give 15-2 as a solid. LC/MS (M+1) calculated: 408.4; observed: 408.0

Workup

  1. customthe cold bath was removed
  2. temperaturethe reaction was cooled to 0° C. in an ice bath
  3. stirringThe reaction was stirred at 0° C. for 30 minutes
  4. temperaturethen warmed to room temperature for 1 hour
  5. customThe reaction was quenched with 1N HCl
  6. stirringby stirring for 3 hours
  7. extractionextracted with chloroform
  8. dry with materialdried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. custompurified

Sources & evidence

ORD record
ord-a31d7dc999274c8f970847b42a72d49a
Source dataset
uspto-grants-2011_08
Patent number
US08008317B2

Reaction notes

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