1,3-Dichloroacetone → (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 1418944Notes

Reaction equation

HRID 1418944 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[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][CH:3]=1.[Cl:22][CH2:23][C:24](=O)[CH2:25]Cl>O1CCOCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[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][CH:3]=1

Participants

4

Reactant 2

HCID 107931,3-DichloroacetoneHCID 86753957(S)-8-chloro-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]-benzodiazepine-1-thiocarboxamide

Product 1

HCID 86753958(S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 8.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A yellow suspension of 7.91 g (0.0248 mol) of (S)-8-chloro-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]-benzodiazepine-1-thiocarboxamide in 160 ml of dioxan was treated with 3.46 g (0.0273 mol) of 1,3-dichloro-2-propanone. The suspension was boiled at reflux for 24 hrs. The suspension obtained was cooled and filtered. The solution was completely freed from the solvents. The crude product was chromatographed over silica gel with cyclohexane/ethyl acetate 1:2 as the eluent and recrystallized from hot acetonitrile. There was obtained 0.85 g (8.7%) of (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one as white crystals; m.p. 221-223 and [α]D20 =-163.0° (MeOH, c=1%).

Workup

  1. temperatureat reflux for 24 hrs
  2. customThe suspension obtained
  3. temperaturewas cooled
  4. filtrationfiltered
  5. customThe crude product was chromatographed over silica gel with cyclohexane/ethyl acetate 1:2 as the eluent
  6. customrecrystallized from hot acetonitrile

Sources & evidence

ORD record
ord-7b3c6c5de6914a129afa7108649a14d0
Source dataset
uspto-grants-1999_03
Patent number
US05885986

Reaction notes

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