Acetic Acid → tert-butyl (1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutyl)carbamate

HRID 2104114Notes

Reaction equation

HRID 2104114 reaction equation
[C:1]([O:5][C:6](=[O:44])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:27]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:26][C:25]4[C:20](=[CH:21][CH:22]=[N:23][C:24]=4[NH:34][NH:35][C:36]([C:38]4[N:39]=[CH:40][N:41]([CH3:43])[CH:42]=4)=O)[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.O1CCOCC1>C(OCC)(=O)C>[CH3:43][N:41]1[CH:42]=[C:38]([C:36]2[N:23]3[C:24]([C:25]4[CH:26]=[C:27]([C:28]5[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=5)[C:18]([C:15]5[CH:16]=[CH:17][C:12]([C:8]6([NH:7][C:6](=[O:44])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:11][CH2:10][CH2:9]6)=[CH:13][CH:14]=5)=[N:19][C:20]=4[CH:21]=[CH:22]3)=[N:34][N:35]=2)[N:39]=[CH:40]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 312751,4-DioxaneHCID 57805467HCID 57805467, compound

Product 1

HCID 57805469tert-butyl (1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutyl)carbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a round bottom flask was added tert-butyl{1-[4-(5-{2-[(1-methyl-1H-imidazol-4-yl)carbonyl]hydrazino}-3-phenyl-1,6-naphthyridin-2-yl)phenyl]cyclobutyl}carbamate (1-7) (2.73 g, 4.63 mmol), acetic acid (5.30 mL, 93 mmol), and 1,4-dioxane (20 mL). The reaction mixture was heated to 80° C. while stirring open to the atmosphere (capped) in a hot oil bath. After 3 hours the reaction mixture was permitted to cool to room temperature, suspended in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography 1-15% IPA/DCM. The appropriate fractions were combined and the solvent was removed in vacuo. The resulting residue was repurified by reverse phase column chromatography (Sunfire C18) eluting with 5 to 95% acetonitrile/(0.1% TFA/water) gradient. The appropriate fractions were free based by suspending in ethyl acetate, washed with a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give tert-butyl (1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutyl)carbamate (1-8) as an off-white solid. MS (M+H)+: observed=572.3, calculated=572.7.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with a saturated solution of sodium bicarbonate
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by silica gel chromatography 1-15% IPA/DCM
  7. customthe solvent was removed in vacuo
  8. customThe resulting residue was repurified by reverse phase column chromatography (Sunfire C18)
  9. washeluting with 5 to 95% acetonitrile/(0.1% TFA/water) gradient
  10. washwashed with a saturated solution of sodium bicarbonate
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-acb8d1f6ede24d80ab5f19a5f204be80
Source dataset
uspto-grants-2009_08
Patent number
US07576209B2

Reaction notes

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