p-Toluenesulfonic acid → HCID 135430722, compound

HRID 1085133Notes

Reaction equation

HRID 1085133 reaction equation
[CH3:1][C:2]1[C:29]([CH3:30])=[CH:28][C:5]2[NH:6][C:7](=S)[CH2:8][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C:25]5[CH:24]=[CH:23][N:22]=[CH:21][C:20]=5[N:19]=[C:18]4[CH3:26])=[CH:13][CH:12]=3)=[N:10][C:4]=2[CH:3]=1.[C:31](OCC)(=[O:34])[NH:32][NH2:33].C1(C)C=CC(S(O)(=O)=O)=CC=1.[H-].[Na+]>C(O)CCC>[CH3:1][C:2]1[C:29]([CH3:30])=[CH:28][C:5]2[N:6]3[C:31](=[O:34])[NH:32][N:33]=[C:7]3[CH:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]4[C:25]5[CH:24]=[CH:23][N:22]=[CH:21][C:20]=5[N:19]=[C:18]4[CH3:26])=[CH:13][CH:12]=3)[NH:10][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 20064Hydrazinecarboxylic acid, ethyl esterHCID 24758Sodium hydrideHCID 10024618HCID 10024618, compound

Product 1

HCID 135430722HCID 135430722, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A solution of 2,3-dihydro-7,8-dimethyl-4-[4-(2-methylimidazo[4,5-c]pyrid-1-yl)phenyl]-1H-[1,5]benzodiazepin-2-thione (411 mg, 1.0 mmol), ethyl carbazate (210 mg, 2 mmol) and p-toluenesulphonic acid (10 mg) in n-butanol (5 ml) was stirred overnight at reflux. The solvent was removed under reduced pressure, and the residue was purified by flash chromatography (etuting with dichloromethane/methanol=9:1). The intermediate carbazate was then dissolved in dry tetrahydrofuran (5 ml) and cyclised by the addition of sodium hydride (60% dispersion in oil, 40 mg, 1 mmol) and stirring for 3 hours at room temperature. The mixture was partitioned between 2N hydrochloric acid (5 ml) and ethyl acetate (20 ml). The aqueous phase was neutralised with saturated aqueous sodium bicarbonate, and extracted with ethyl acetate:tetrahydrofuran=1:1 (2×30 ml). The extracts were combined, dried (MgSO4), and concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with dichloromethane:methanol=10:1). The product was further purified by recrystallisation from methanol/dichloromethane to give a white solid, (85 mg, 20%), m.p.>325° C.

Workup

  1. temperatureat reflux
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was purified by flash chromatography (etuting with dichloromethane/methanol=9:1)
  4. dissolutionThe intermediate carbazate was then dissolved in dry tetrahydrofuran (5 ml)
  5. customThe mixture was partitioned between 2N hydrochloric acid (5 ml) and ethyl acetate (20 ml)
  6. extractionextracted with ethyl acetate
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (eluting with dichloromethane:methanol=10:1)
  10. customThe product was further purified by recrystallisation from methanol/dichloromethane
  11. customto give a white solid, (85 mg, 20%), m.p.>325° C.

Sources & evidence

ORD record
ord-1690fe23e39041c8be89e8aeede9b508
Source dataset
uspto-grants-1991_04
Patent number
US05008263

Reaction notes

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