Cyanogen Bromide → 9-[4-(1-Aminocyclobutyl)phenyl]-8-phenyl[1,2,4]triazolo[4,3-h]-1,7-naphthyridin-3-amine

HRID 1914824Notes

Reaction equation

HRID 1914824 reaction equation
[NH:1]([C:3]1[N:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[C:10]([C:13]1[CH:18]=[CH:17][C:16]([C:19]3([NH:23]C(=O)OC(C)(C)C)[CH2:22][CH2:21][CH2:20]3)=[CH:15][CH:14]=1)[C:9]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[CH:8]2)[NH2:2].[N:37]#[C:38]Br>C(O)C.CCOC(C)=O>[NH2:23][C:19]1([C:16]2[CH:15]=[CH:14][C:13]([C:10]3[C:9]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:8][C:7]4[CH:6]=[CH:5][N:4]5[C:38]([NH2:37])=[N:2][N:1]=[C:3]5[C:12]=4[N:11]=3)=[CH:18][CH:17]=2)[CH2:22][CH2:21][CH2:20]1

Participants

5

Reactant 2

HCID 10476Cyanogen BromideHCID 58034319Tert-butyl {1-[4-(8-hydrazino-3-phenyl-1,7-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 469402299-[4-(1-Aminocyclobutyl)phenyl]-8-phenyl[1,2,4]triazolo[4,3-h]-1,7-naphthyridin-3-amine

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of tert-butyl {1-[4-(8-hydrazino-3-phenyl-1,7-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate (7-5) (30 mg, 0.0620 mmol), cyanogen bromide (19.8 mg, 0187 mmol) in ethanol (2 mL) was stirred at 60° C. for 72 hours. The mixture was diluted with AcOEt, washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography on silica gel. The residue was treated with HCl in MeOH and the mixture was heated in a microwave reactor at 80° C. for 5 min. The solvent was evaporated and the residue was purified by reverse phase HPLC (H2O/0.1% TFA aq.-MeCN/0.1% TFA aq.) to give 9-[4-(1-aminocyclobutyl)phenyl]-8-phenyl[1,2,4]triazolo[4,3-h]-1,7-naphthyridin-3-amine (8-1) as a pale yellow solid.

Workup

  1. washwashed with water
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel
  6. additionThe residue was treated with HCl in MeOH
  7. temperaturethe mixture was heated in a microwave reactor at 80° C. for 5 min
  8. customThe solvent was evaporated
  9. customthe residue was purified by reverse phase HPLC (H2O/0.1% TFA aq.-MeCN/0.1% TFA aq.)

Sources & evidence

ORD record
ord-6511dbb7680944029fe548519c0d36d9
Source dataset
uspto-grants-2013_12
Patent number
US08614221B2

Reaction notes

Loading…