p-Toluenesulfonic acid → (E)-5,6,9,10-Tetrahydro-10-[(5-methyl-1H-imidazol-4-yl)methylene]-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one

HRID 727797Notes

Reaction equation

HRID 727797 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH:13]1[CH:25]=[CH:24][C:23]2[CH2:26][CH2:27][CH2:28][N:21]3[C:22]=2[C:14]=1[C:15]1[C:16](=[O:29])[CH2:17][CH2:18][CH2:19][C:20]=13.[CH3:30][C:31]1[N:35](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:34]=[N:33][C:32]=1[CH:55]=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C(O)(=O)C>[CH3:30][C:31]1[NH:35][CH:34]=[N:33][C:32]=1/[CH:55]=[C:17]1\[CH2:18][CH2:19][C:20]2[N:21]3[CH2:28][CH2:27][CH2:26][C:23]4[CH:24]=[CH:25][CH:13]=[C:14]([C:15]=2[C:16]\1=[O:29])[C:22]3=4

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 7912DiisopropylamineHCID 12347665,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-oneHCID 118243385-methyl-1-trityl-1H-imidazole-4-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 70055365(E)-5,6,9,10-Tetrahydro-10-[(5-methyl-1H-imidazol-4-yl)methylene]-4H-pyrido[3,2,1-jk]carbazol-11(8H)-oneYield 220.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

n-Butyllithium (1.73M in hexane; 4.14 ml) was added dropwise to a cold (-70°) stirred solution of diisopropylamine (1 ml) in dry THF (10 ml) under nitrogen. The resulting solution was stirred at 0° for 30 min, cooled to -70° and added dropwise to a cold (-70°) stirred suspension of 5,6,9,10-tetrahydro-4H-pyrido[3,2,1-jk]carbazol-11(8H)-one (645 mg) in dry THF (20 ml) under nitrogen. The solution was allowed to reach 0° over 1 h, cooled to -70° and a solution of 5-methyl-1-(triphenylmethyl)-1H-imidazole-4-carboxaldehyde (1.01 g) in dry THF (10 ml) was added dropwise. The stirred mixture was allowed to reach room temperature over 2 h, and then stirred for a further 3 h. The solution was cooled to -70° and treated with acetic acid (8 ml) and p-toluenesulphonic acid (5.44 g) and heated at reflux for 16 h. The solvent was removed in vacuo, the residue was treated with 8% sodium bicarbonate solution (150 ml) and extracted with dichloromethane (4×50 ml). The combined, dried organic extracts were evaporated to give a gum (ca. 2 g) which was purified by FCC eluting with System A to give the title compound (145 mg) as a solid, m.p. 260°-264°.

Workup

  1. temperaturecooled to -70°
  2. additionadded dropwise to a cold (-70°)
  3. stirringstirred
  4. waitto reach 0° over 1 h
  5. temperaturecooled to -70°
  6. waitto reach room temperature over 2 h
  7. stirringstirred for a further 3 h
  8. temperatureThe solution was cooled to -70°
  9. temperatureheated
  10. temperatureat reflux for 16 h
  11. customThe solvent was removed in vacuo
  12. additionthe residue was treated with 8% sodium bicarbonate solution (150 ml)
  13. extractionextracted with dichloromethane (4×50 ml)
  14. customdried organic extracts were evaporated

Sources & evidence

ORD record
ord-2008f7d8ed66445d81daadc68d4608b9
Source dataset
uspto-grants-1991_09
Patent number
US05045545

Reaction notes

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