Hydrochloric Acid → 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

HRID 221980Notes

Reaction equation

HRID 221980 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:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)[C:14]([C:20]5[CH:25]=[CH:24][C:23]([C:26]6([NH2:34])[CH2:29][C:28]7(OCC[O:30]7)[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.[O:41]=[C:42]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:44](=[O:51])N1C(OCC)=O.CCN(C(C)C)C(C)C.Cl>C(Cl)(Cl)Cl.CO.CN(C=O)C>[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:35]5[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=5)[C:14]([C:20]5[CH:21]=[CH:22][C:23]([C:26]6([N:34]7[C:42](=[O:41])[C:50]8[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=8)[C:44]7=[O:51])[CH2:29][C:28](=[O:30])[CH2:27]6)=[CH:24][CH:25]=5)=[N:15][C:16]=4[CH:17]=[CH:18]3)=[N:9][N:8]=2)[N:4]=[CH:3]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 31187N-CarbethoxyphthalimideHCID 81531DiisopropylethylamineHCID 248095872-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}-5,8-dioxaspiro[3.4]octan-2-amine

Product 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

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}-5,8-dioxaspiro[3.4]octan-2-amine (142) (1.3 g, 2.49 mmol) and ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate (0.37 g, 2.49 mmol) in CHCl3 (5 mL) was stirred at 70° C. for overnight. The mixture and DMF (5 mL) and DIPEA (0.44 mL, 2.49 mmol) were heated under microwave irradiation at 150° C. for 1 hour. The solvent was removed under reduced pressure, and to the residue was added MeOH. The resulting solid was collected by filtration. The solid (100 mg, 0.152 mmol) and 6N HCl in MeOH (1 mL) was stirred at room temperature for 1 hour. The mixture was quenched by aq. NaHCO3, extracted with CHCl3, dried (MgSO4), filtered, and concentrated under reduced pressure to yield (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). MS (M+H)+: observed 616, calculated=616.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionto the residue was added MeOH
  3. filtrationThe resulting solid was collected by filtration
  4. customThe mixture was quenched by aq. NaHCO3
  5. extractionextracted with CHCl3
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e845706c4d27457e82230666d54f3e11
Source dataset
uspto-grants-2012_06
Patent number
US08207169B2

Reaction notes

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