1,2-Dichloroethane → 1-[4-(3-Methyl-8-phenyl[1,2,4]triazolo[4,3-h]-1,7-naphthyridin-9-yl)phenyl]cyclobutanamine

HRID 1914825Notes

Reaction equation

HRID 1914825 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].[C:37](O)(=O)[CH3:38].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN1C(=O)CCC1.CCOC(C)=O>[CH3:37][C:38]1[N:4]2[CH:5]=[CH:6][C:7]3[CH:8]=[C:9]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:10]([C:13]4[CH:18]=[CH:17][C:16]([C:19]5([NH2:23])[CH2:22][CH2:21][CH2:20]5)=[CH:15][CH:14]=4)=[N:11][C:12]=3[C:3]2=[N:1][N:2]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 58034319Tert-butyl {1-[4-(8-hydrazino-3-phenyl-1,7-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate

Product 1

HCID 580345251-[4-(3-Methyl-8-phenyl[1,2,4]triazolo[4,3-h]-1,7-naphthyridin-9-yl)phenyl]cyclobutanamine

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To 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), acetic acid (11.2 mg, 0.187 mmol), HOBt (19.1 mg, 0.125 mmol) and DIPEA (0.044 mL, 0.249 mmol) in NMP (2 mL) was added EDC (219 mg, 0.125 mmol). The mixture was stirred at room temperature for 30 min and then at 100° 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 silica gel chromatography. HCl in MeOH was added to the residue and the mixture was heated in a microwave reactor at 80° C. for 5 minutes. 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 1-[4-(3-methyl-8-phenyl[1,2,4]triazolo[4,3-h]-1,7-naphthyridin-9-yl)phenyl]cyclobutanamine (9-1) as a pale yellow solid.

Workup

  1. waitat 100° C. for 72 hours
  2. washwashed with water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. additionHCl in MeOH was added to the residue
  8. temperaturethe mixture was heated in a microwave reactor at 80° C. for 5 minutes
  9. customThe solvent was evaporated
  10. customthe residue was purified by reverse phase HPLC (H2O/0.1% TFA aq.-MeCN/0.1% TFA aq.)

Sources & evidence

ORD record
ord-697b57af64c04482aac08171e4d99bee
Source dataset
uspto-grants-2013_12
Patent number
US08614221B2

Reaction notes

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