Acetic Acid → 2-(4-Chloro-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(2-dimethylamino-1-methyl-ethyl)-1H-1,3,6-triaza-s-indacene-5,7-dione

HRID 929133Notes

Reaction equation

HRID 929133 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[N+:11]([O-])=O)[C:7](=[O:14])[N:6]([CH:15]([CH3:20])[CH2:16][N:17]([CH3:19])[CH3:18])[C:5]2=[O:21].[CH3:22][C:23](O)=O.[ClH:26].[CH3:27][OH:28]>O1CCOCC1.O.[Pd]>[Cl:26][C:9]1[CH:10]=[CH:2][NH:1][C:27](=[O:28])[C:23]=1[C:22]1[NH:1][C:2]2[C:10]([N:11]=1)=[CH:9][C:8]1[C:7](=[O:14])[N:6]([CH:15]([CH3:20])[CH2:16][N:17]([CH3:19])[CH3:18])[C:5](=[O:21])[C:4]=1[CH:3]=2

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 887MethanolHCID 667934325-Amino-2-(2-dimethylamino-1-methyl-ethyl)-6-nitro-isoindole-1,3-dione

Product 1

HCID 1363511972-(4-Chloro-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(2-dimethylamino-1-methyl-ethyl)-1H-1,3,6-triaza-s-indacene-5,7-dioneYield 80%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

The mixture of 5-amino-2-(2-dimethylamino-1-methyl-ethyl)-6-nitro-isoindole-1,3-dione (585 mg, 2.0 mmol) and Pd/C (60 mg) in MeOH (95 mL) was stirred under atmospheric H2 for 2.5 h and filtered through Celite. The filtrate was mixed with 4-chloro-2-methoxynicotinic aldehyde (343.2 mg, 2.0 mmol) and HOAc (5 mL), stirred at the room temperature for 62 h, and evaporated under reduced pressure to afford an oil crude which was mixed with HCl in dioxane (4 M, 25 mL) and H2O (2 mL), heated at 70° C. for 1 h and evaporated. The residue was diluted with a mixed solvent of MeOH/DCM (50 mL/50 mL), basified with 28% aqueous NH4OH, and concentrated. Chromatography of the residue with CH2Cl2/MeOH/28% aqueous NH4OH (60:10:1) afforded the title compound (642 mg, 80%). 1H NMR (DMSO-d6) δ 1.39 (d, J=6 Hz, 3H, CH3), 2.14 (s, 6H, 2CH3), 2.29 (m, 1H), 3.04 (m, 1H), 4.40 (m, 1H), 6.59 (d, J=8 Hz, 1H), 7.69 (d, J=8 Hz, 1H), 8.04 (s, 1H), 8.05 (s, 1H); ESI-MS m/z 400.3 (MH+).

Workup

  1. filtrationfiltered through Celite
  2. stirringstirred at the room temperature for 62 h
  3. customevaporated under reduced pressure
  4. customto afford an oil crude which
  5. customevaporated
  6. additionThe residue was diluted with a mixed solvent of MeOH/DCM (50 mL/50 mL)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-b9626e8db0b74f5dabf151fe0f4966e0
Source dataset
uspto-grants-2016_03
Patent number
US09290503B2

Reaction notes

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