p-Toluenesulfonic acid → HCID 15203933, compound

HRID 1085134Notes

Reaction equation

HRID 1085134 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.CO[CH:33](OC)[CH2:34][NH2:35].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C(O)CCC.S(=O)(=O)(O)O>[CH3:1][C:2]1[C:29]([CH3:30])=[CH:28][C:5]2[N:6]3[CH:33]=[CH:34][N:35]=[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

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 89728Aminoacetaldehyde dimethyl acetalHCID 516892Sodium BicarbonateHCID 10024618HCID 10024618, compound

Product 1

HCID 15203933HCID 15203933, compound

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,3-dihydro-7,8-dimethyl-4-[4-(2-methylimidazo[4,5-c]pyrid-1-yl)phenyl]-1H-[1,5]benzodiazepin-2-thione (575 mg. 1.4 mmol), aminoacetaldehyde dimethyl acetal (294 mg, 2.8 mmol), and p-toluenesulphonic acid (14 mg) in n-butanol (7 ml) was heated at reflux for 8 hours under nitrogen. The solvent was removed under reduced pressure, and the residue was purified by flash chromatography (eluting with ethyl acetate/methanol=6:1). The intermediate thus obtained was dissolved in concentrated sulphuric acid (5 ml) and heated at 100° C. for 20 minutes. The mixture was cooled and poured onto ice, and then neutralised with saturated aqueous sodium bicarbonate. The product was extracted into dichloromethane (2×150 ml), and the combined extracts were dried (MgSO4) and concentrated under reduced pressure. Purification by flash chromatography (eluting with ethyl acetate:methanol=6:1) gave the title compound as a buff solid, (180 mg, 31%), m.p. 193°-195° C. after dissolution in methanol and precipitation with acetone.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 8 hours under nitrogen
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by flash chromatography (eluting with ethyl acetate/methanol=6:1)
  5. customThe intermediate thus obtained
  6. temperatureThe mixture was cooled
  7. additionpoured onto ice
  8. extractionThe product was extracted into dichloromethane (2×150 ml)
  9. dry with materialthe combined extracts were dried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. customPurification
  12. washby flash chromatography (eluting with ethyl acetate:methanol=6:1)

Sources & evidence

ORD record
ord-46d0b539b01647e29d280d1185cf5d89
Source dataset
uspto-grants-1991_04
Patent number
US05008263

Reaction notes

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