Sodium Iodide → HCID 69946958, compound

HRID 1416927Notes

Reaction equation

HRID 1416927 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH2:9][CH2:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=2.C[O:21][C:22](=[O:35])[C:23]1[CH:28]=[CH:27][CH:26]=[N:25][C:24]=1[N:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[OH-].[Na+]>C(O)C.O.C1(C)C=CC=CC=1.CC(=O)CC>[ClH:1].[ClH:1].[CH:16]1[C:7]2[CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:5]([CH2:4][CH2:3][CH2:2][N:32]3[CH2:33][CH2:34][N:29]([C:24]4[C:23]([C:22]([OH:35])=[O:21])=[CH:28][CH:27]=[CH:26][N:25]=4)[CH2:30][CH2:31]3)[C:6]=2[CH:19]=[CH:18][CH:17]=1

Participants

10

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 2867795-(3-Chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepineHCID 20132428Methyl 2-(piperazin-1-yl)pyridine-3-carboxylate

Product 1

HCID 69946958HCID 69946958, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6569Methyl Ethyl KetoneSolvent

Procedure

A mixture of 5-(3-chloropropyl)-10,11-dihydro-5H-dibenz[b,f]azepine (4.54 g, 16.7 mmol), 2-piperazinylnicotinic acid methyl ester 3.7 g, 16.7 mmol), dry potassium carbonate (6.92 g, 50.1 mmol), sodium iodide (2.5 g, 16.7 mmol) and 2-butanone (50 ml) was heated at reflux temperature for 60 h. After cooling to room temperature, toluene (100 ml) and water (100 ml) were added. The organic layer was separated, washed with water (2×50 ml) and evaporated in vacuo. The crude product was purified by column chromatography on silica gel using a mixture of toluene and ethyl acetate (3:1) containing triethylamine (2.5%) as eluent. This afforded 2.3 g (30%) of 2-(4-(3-(10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propyl)-1-piperazinyl)-3-pyridinecarboxylic acid methyl ester as an oil. A mixture of the above ester (2.3 g, 5.04 mmol) dissolved in a mixture of 2 N sodium hydroxide (8.32 ml, 16.63 mmol) and ethanol (25 ml) was stirred at room temperature for 16 h. The ethanol was evaporated in vacuo, and the remainder was diluted with water (50 ml). 2 N Hydrochloric acid (20 ml) was added, and the solution was washed with diethyl ether (25 ml). The aqueous phase was extracted with dichloromethane (3×30 ml). The combined organic extracts were dried (MgSO4) and evaporated in vacuo to afford a foam. This was crystallized from tetrahydrofuran, filtered and dried, affording 1.20 g (50%) of the title compound.

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 60 h
  3. customThe organic layer was separated
  4. washwashed with water (2×50 ml)
  5. customevaporated in vacuo
  6. customThe crude product was purified by column chromatography on silica gel using
  7. additiona mixture of toluene and ethyl acetate (3:1)
  8. additioncontaining triethylamine (2.5%) as eluent
  9. customThe ethanol was evaporated in vacuo
  10. additionthe remainder was diluted with water (50 ml)
  11. addition2 N Hydrochloric acid (20 ml) was added
  12. washthe solution was washed with diethyl ether (25 ml)
  13. extractionThe aqueous phase was extracted with dichloromethane (3×30 ml)
  14. dry with materialThe combined organic extracts were dried (MgSO4)
  15. customevaporated in vacuo
  16. customto afford a foam
  17. customThis was crystallized from tetrahydrofuran
  18. filtrationfiltered
  19. customdried

Sources & evidence

ORD record
ord-6aa987ee1abb4a3abe8e3d740b53709e
Source dataset
uspto-grants-1999_06
Patent number
US05916889

Reaction notes

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