HCID 178471518, compound → HCID 4192174, compound

HRID 566287Notes

Reaction equation

HRID 566287 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][CH:13]([CH:16](OCC)OCC)[CH2:14][OH:15])[CH2:9][N:8]=[C:7]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[C:6]=2[CH:30]=1>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:16]=[C:13]([CH2:14][OH:15])[N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[C:6]=2[CH:30]=1

Participants

3

Reactant 1

HCID 178471518HCID 178471518, compound

Product 1

HCID 4192174HCID 4192174, compoundYield 49.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 30 g of 7-chloro-2-(3,3-diethoxy-1-hydroxy-2-propyl-amino)-5-(2-fluorophenyl)-3H-1,4-benzodiazepine in 300 ml of glacial acetic acid was heated to reflux temperature for 5 h. After cooling the solvent was removed in a vacuum, the residue was taken up in 300 ml of ethanol, the solution was treated with 150 ml of 2N aqueous sodium hydroxide solution and left te stand at room temperature for 2 h. Then, about 200 ml of ethanol were distilled off at 30° C. in a vacuum. The solution remaining behind was extracted three times with chloroform. The chloroform extracts were washed with saturated sodium chloride solution, then dried over sodium sulphate and evaporated to dryness in a vacuum. The residue (20.5 g) was dissolved in chloroform and chromatographed over 500 g of silica gel. Byproducts (total 4.1 g) were eluted with chloroform containing 0.2% to 1.6% ethanol. 13.0 g of the desired product were eluted with chloroform containing 2.4 to 20% ethanol. After recrystallization from ethyl acetate/diethyl ether there were obtained 11.6 g of 8-chloro-6-(2-fluorophenyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-2-methanol of m.p. 196-199.5° C. After repeated recrystallization from ethyl acetate the m.p. lay at 199-201° C.

Workup

  1. temperatureto reflux temperature for 5 h
  2. temperatureAfter cooling the solvent
  3. customwas removed in a vacuum
  4. additionthe solution was treated with 150 ml of 2N aqueous sodium hydroxide solution
  5. distillationThen, about 200 ml of ethanol were distilled off at 30° C. in a vacuum
  6. extractionThe solution remaining behind was extracted three times with chloroform
  7. washThe chloroform extracts were washed with saturated sodium chloride solution
  8. dry with materialdried over sodium sulphate
  9. customevaporated to dryness in a vacuum
  10. dissolutionThe residue (20.5 g) was dissolved in chloroform
  11. customchromatographed over 500 g of silica gel
  12. washByproducts (total 4.1 g) were eluted with chloroform containing 0.2% to 1.6% ethanol
  13. wash13.0 g of the desired product were eluted with chloroform containing 2.4 to 20% ethanol
  14. customAfter recrystallization from ethyl acetate/diethyl ether there

Sources & evidence

ORD record
ord-3665cdef00b04a4db3c1ec76ae6b43f1
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

Loading…