1,3-Dichloroacetone → (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 1737363Notes

Reaction equation

HRID 1737363 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]3[CH2:21][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:23][CH2:24][C:25](=O)[CH2:26]Cl>O1CCOCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]3[CH2:21][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:26]=[C:25]([CH2:24][Cl:23])[N:17]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 107931,3-DichloroacetoneHCID 53664939(S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-thiocarboxamide

Product 1

HCID 70067673(S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-oneYield 58%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A suspension of 6.8 g (0.0204 mol) of (S)-8-chloro-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-thiocarboxamide in 100 ml of dioxan was treated with 2.85 g (0.0224 mol) of 1,3-dichloro-2-propanone and boiled at reflux for 48 hrs. After cooling 30 g of silica gel were added and the mixture was stirred for a further 1 hr. The mixture was concentrated in a water-jet vacuum and dried in a high vacuum. The crude product, adsorbed on silica gel, was applied to a silica gel column equilibrated with ethyl acetate and then eluted with ethyl acetate. There were obtained 4.7 g (58%) of (S)-8-chloro-1-(4-chloromethyl-thiazol-2-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one in the form of white crystals.

Workup

  1. temperatureat reflux for 48 hrs
  2. temperatureAfter cooling 30 g of silica gel
  3. additionwere added
  4. concentrationThe mixture was concentrated in a water-jet vacuum
  5. customdried in a high vacuum
  6. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-3d4292667b1645a390d4b913c33ec67c
Source dataset
uspto-grants-1999_10
Patent number
US05962450

Reaction notes

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