Hydrochloric Acid → 7-nitro-6-(4-o-tolyl-piperazin-1-yl)-2H-isoquinolin-1-one

HRID 1481870Notes

Reaction equation

HRID 1481870 reaction equation
[CH3:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])[CH2:13][CH2:12]2)[C:8]([N+:24]([O-:26])=[O:25])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH3:27]OC(OC)N(C)C.CC(C)([O-])C.[K+].Cl>CC1CCCO1.C1COCC1>[N+:24]([C:8]1[CH:7]=[C:3]2[C:2]([CH:1]=[CH:27][NH:6][C:4]2=[O:5])=[CH:10][C:9]=1[N:11]1[CH2:12][CH2:13][N:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH3:23])[CH2:15][CH2:16]1)([O-:26])=[O:25]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 78373Dimethylformamide dimethyl acetalHCID 23665647Potassium tert-butoxideHCID 896905162-Methyl-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzamide

Product 1

HCID 896906327-nitro-6-(4-o-tolyl-piperazin-1-yl)-2H-isoquinolin-1-one

Reagents, catalysts & solvents 2

HCID 73012-MethyltetrahydrofuranSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 2-methyl-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzamide (3.0 g, 8.46 mmol) and dimethylformamide dimethyl acetal (1.32 g, 11.08 mmol) in 2-methyl tetrahydrofuran (60 mL) were heated in a Dean stark apparatus at 105° C. for 30 min. The progress of the reaction was monitored by LCMS. The volume of the reaction was reduced to half and the reaction mass was cooled to 55° C. A solution of potassium tert-butoxide (1.44 g, 12.8 mL, 12.86 mmol) in THF (1 M) was added dropwise over a period of 30 min. The reaction mixture was allowed to heat at 65° C. overnight. After completion of the reaction, solvent was removed in vacuo, residue obtained was acidified with 1.5 N HCl. The aqueous layer was extracted in dichloromethane (5×75 mL). The combined extract was washed with water, brine solution and dried over anhydrous Na2SO4. The crude product obtained was purified by the flash column chromatography (230-400 size mesh) using 1.0-1.25% methanol in dichloromethane to afford the compound 7-nitro-6-(4-o-tolyl-piperazin-1-yl)-2H-isoquinolin-1-one. Yield (0.25 g, 8.3%; and reddish brown solid).

Workup

  1. temperaturethe reaction mass was cooled to 55° C
  2. temperatureto heat at 65° C. overnight
  3. customAfter completion of the reaction, solvent
  4. customwas removed in vacuo, residue
  5. customobtained
  6. extractionThe aqueous layer was extracted in dichloromethane (5×75 mL)
  7. extractionThe combined extract
  8. washwas washed with water, brine solution
  9. dry with materialdried over anhydrous Na2SO4
  10. customThe crude product obtained
  11. customwas purified by the flash column chromatography (230-400 size mesh)

Sources & evidence

ORD record
ord-00e22989304e44fda5b1dc3049853b69
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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