Sodium Carbonate → Methyl [(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-thioxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetate

HRID 628967Notes

Reaction equation

HRID 628967 reaction equation
P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:2].C([O-])([O-])=O.[Na+].[Na+].[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[C:34]3[CH:35]=[C:36]([O:39][CH3:40])[CH:37]=[CH:38][C:33]=3[NH:32][C:31](=O)[C@H:30]([CH2:42][C:43]([O:45][CH3:46])=[O:44])[N:29]=2)=[CH:24][CH:23]=1>ClCCCl>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[C:34]3[CH:35]=[C:36]([O:39][CH3:40])[CH:37]=[CH:38][C:33]=3[NH:32][C:31](=[S:2])[C@H:30]([CH2:42][C:43]([O:45][CH3:46])=[O:44])[N:29]=2)=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 14817Phosphorus sulfide (P2S5)HCID 53261361(S)-methyl 2-(5-(4-chlorophenyl)-7-methoxy-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)acetate

Product 1

HCID 57465560Methyl [(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-thioxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetateYield 98%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of P4S10 (36.1 g, 81.1 mmol) and Na2CO3 (8.6 g, 81.1 mmol) in 1,2-DCE (700 ml) at room temperature was stirred for 2 h before methyl [(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-oxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetate (for a preparation see Reference compound D) (16.8 g, 45.1 mmol) was added. The resulting mixture was stirred at 70° C. for 2 h before being cooled and filtered. The solid was washed twice with DCM and the filtrate washed with sat. Sodium hydrogen carbonate and brine. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash-chromatography on silica gel (DCM/MeOH: 99/1) to afford the title compound (17.2 g, 98% yield) as a yellowish solid. LC/MS (Method D): m/z 389 [M(35Cl)+H]+, Rt 2.64 min

Workup

  1. additionwas added
  2. temperaturebefore being cooled
  3. filtrationfiltered
  4. washThe solid was washed twice with DCM
  5. washthe filtrate washed with sat. Sodium hydrogen carbonate and brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash-chromatography on silica gel (DCM/MeOH: 99/1)

Sources & evidence

ORD record
ord-6a90d204a404488ea951a0d3e09fb0b2
Source dataset
uspto-grants-2016_04
Patent number
US09315487B2

Reaction notes

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