Acetic Acid → HCID 89690418, compound

HRID 1481865Notes

Reaction equation

HRID 1481865 reaction equation
C(O)C.C(O)(=O)C.[CH3:8][N:9]([CH2:11][C:12]1[CH:13]=[C:14]([CH:43]=[CH:44][CH:45]=1)[CH2:15][N:16]1[CH2:25][CH2:24][C:23]2[C:18](=[CH:19][C:20]([N+:39]([O-])=O)=[C:21]([N:26]3[CH2:31][CH2:30][N:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH3:38])[CH2:28][CH2:27]3)[CH:22]=2)[C:17]1=[O:42])[CH3:10]>[Fe]>[NH2:39][C:20]1[CH:19]=[C:18]2[C:23]([CH2:24][CH2:25][N:16]([CH2:15][C:14]3[CH:43]=[CH:44][CH:45]=[C:12]([CH2:11][N:9]([CH3:10])[CH3:8])[CH:13]=3)[C:17]2=[O:42])=[CH:22][C:21]=1[N:26]1[CH2:27][CH2:28][N:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[CH3:38])[CH2:30][CH2:31]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 89690658HCID 89690658, compound

Product 1

HCID 89690418HCID 89690418, compound

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Conditions

Temperature
75 °C

Procedure

In a 100 ml round bottom flask equipped with a magnetic stir bar and fitted with a septum with a nitrogen inlet, the iron powder (382.70 mg, 6.85 mmol) was suspended in clean, dry, reagent-grade ethanol (30.00 ml, 513.81 mmol) under nitrogen and at room temperature. To the stirred reaction was added the acetic acid (3.00 ml, 52.40 mmol) and the mixture was stirred to ensure homogeneity. The 2-(3-dimethylaminomethyl-benzyl)-7-nitro-6-(4-o-tolyl-piperazin-1-yl)-3,4-dihydro-2H-isoquinolin-1-one 11a (140.80 mg, 0.27 mmol) was then added in one portion and the reaction was warmed to 75° C. and allowed to stir under nitrogen for 4 h. After 4 h, the reaction was cooled to room temperature and the reaction solution was filtered through Celite, eluting heavily with methanol. The collected solution was then concentrated under reduced pressure and the solvent was removed under reduced pressure. The resultant red oil was taken up in 50 ml of ethyl acetate and washed with 50 ml of saturated NaHCO3 (aq) solution. The product was then extracted from the aqueous using ethyl acetate (3×30 ml) and the organic phases were combined and washed with brine (1×100 ml). The solution was then dried over Na2SO4; the solution was decanted and the solvent was removed under reduced pressure. The resultant brown solid was then purified using silica gel column chromatography, eluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane. 7-amino-2-(3-dimethylaminomethyl-benzyl)-6-(4-o-tolyl-piperazin-1-yl)-3,4-dihydro-2H-isoquinolin-1-one 1 b (73.70 mg, 0.15 mmol) was isolated as a tan solid and was carried on without further purifications. LCMS (m/e)=483 (M+H).

Workup

  1. customIn a 100 ml round bottom flask equipped with a magnetic stir bar
  2. customfitted with a septum with a nitrogen inlet
  3. customdry
  4. customat room temperature
  5. customTo the stirred reaction
  6. stirringto stir under nitrogen for 4 h
  7. temperaturethe reaction was cooled to room temperature
  8. filtrationthe reaction solution was filtered through Celite
  9. washeluting heavily with methanol
  10. concentrationThe collected solution was then concentrated under reduced pressure
  11. customthe solvent was removed under reduced pressure
  12. washwashed with 50 ml of saturated NaHCO3 (aq) solution
  13. extractionThe product was then extracted from the
  14. washwashed with brine (1×100 ml)
  15. dry with materialThe solution was then dried over Na2SO4
  16. customthe solution was decanted
  17. customthe solvent was removed under reduced pressure
  18. customThe resultant brown solid was then purified
  19. washeluting a gradient of 100% dichloromethane to 10% MeOH in dichloromethane

Sources & evidence

ORD record
ord-4911311f6acf4919a3712a39456cb287
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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