1,3-Dichloroacetone → 7-chloro-3-(4-chloromethyl-thiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1737378Notes

Reaction equation

HRID 1737378 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([CH3:19])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](=[S:18])[NH2:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[F:21].[Cl:22][CH2:23][C:24](=O)[CH2:25]Cl>O1CCOCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([CH3:19])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[S:18][CH:25]=[C:24]([CH2:23][Cl:22])[N:17]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[F:21]

Participants

4

Reactant 2

HCID 107931,3-Dichloroacetone2×HCID 21842257HCID 21842257, compound

Product 1

HCID 218422927-chloro-3-(4-chloromethyl-thiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-oneYield 35.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A yellow suspension of 2.45 g (0.00754 mol) of 7-chloro-8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-thiocarboxamide in 130 ml of dioxan was treated with 1.05 g (0.00829 mol) of 1,3-dichloro-2-propanone. The suspension was boiled at reflux for 20 hrs. and cooled. A further 1.05 g (0.00829 mol) of 1,3-dichloro-2-propanone and 60 ml of dioxan were added and the solution was boiled at reflux for a further 16 hrs. The solution was cooled and completely freed from the solvents. The residue was chromatographed over silica gel with cyclohexane/ethyl acetate 1:2 as the eluent and recrystallized from hot acetonitrile. There were obtained 1.05 g (35%) of 7-chloro-3-(4-chloromethyl-thiazol-2-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one as white crystals; m.p. 234-235°.

Workup

  1. temperatureat reflux for 20 hrs
  2. temperatureand cooled
  3. temperatureat reflux for a further 16 hrs
  4. temperatureThe solution was cooled
  5. customThe residue was chromatographed over silica gel with cyclohexane/ethyl acetate 1:2 as the eluent
  6. customrecrystallized from hot acetonitrile

Sources & evidence

ORD record
ord-9b70422eff9948a3a6fdae9369098fd2
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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