Methanol → 3,3-dimethoxy-1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutanamine

HRID 221981Notes

Reaction equation

HRID 221981 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:19]3[C:10]([C:11]4[CH:12]=[C:13]([C:42]5[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=5)[C:14]([C:20]5[CH:25]=[CH:24][C:23]([C:26]6([N:31]7C(=O)C8C(=CC=CC=8)C7=O)[CH2:29][C:28](=[O:30])[CH2:27]6)=[CH:22][CH:21]=5)=[N:15][C:16]=4[CH:17]=[CH:18]3)=[N:9][N:8]=2)[N:4]=[CH:3]1.[C:48](O)(C(F)(F)F)=[O:49].O.NN.[CH3:58]O>>[CH3:58][O:30][C:28]1([O:49][CH3:48])[CH2:29][C:26]([C:23]2[CH:24]=[CH:25][C:20]([C:14]3[C:13]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[CH:12][C:11]4[C:10]5=[N:9][N:8]=[C:7]([C:5]6[N:4]=[CH:3][N:2]([CH3:1])[CH:6]=6)[N:19]5[CH:18]=[CH:17][C:16]=4[N:15]=3)=[CH:21][CH:22]=2)([NH2:31])[CH2:27]1

Participants

5

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 24654Hydrazine hydrate (1:1)HCID 582298522-(1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}-3-oxocyclobutyl)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 671175283,3-dimethoxy-1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutanamine

Conditions

Temperature
100 °C

Procedure

To a micro reactor vessel was added (2-(1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}-3-oxocyclobutyl)-1H-isoindole-1,3(2H)-dione (1-13) (100 mg, 0.162 mmol), TFA (1 mL), and MeOH (5 mL), and the mixture was heated under microwave irradiation at 100° C. for 10 minutes. Then hydrazine hydrate (80 mg, 1.6 mmol) was added, and the mixture was heated under microwave irradiation at 100° C. for 10 minutes. The solvent was concentrated under reduced pressure, and the residue was purified 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 3,3-dimethoxy-1-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}cyclobutanamine (1-18). HRMS (M+H)+: observed=532.2461, calculated=532.2466.

Workup

  1. temperaturethe mixture was heated under microwave irradiation at 100° C. for 10 minutes
  2. concentrationThe solvent was concentrated under reduced pressure
  3. customthe residue was purified by reverse phase column chromatography (Sunfire C18)
  4. washeluting with 5 to 95% acetonitrile/(0.1% TFA/water) gradient
  5. washwashed with a saturated solution of sodium bicarbonate
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2b2720c678bd4c1cb3fa4ade4e296c0c
Source dataset
uspto-grants-2012_06
Patent number
US08207169B2

Reaction notes

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