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

HRID 570164Notes

Reaction equation

HRID 570164 reaction equation
P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:2].C([O-])([O-])=O.[Na+].[Na+].[CH3:21][O:22][C:23](=[O:46])[CH2:24][C@@H:25]1[N:31]=[C:30]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[C:29]2[CH:39]=[C:40]([O:43][CH3:44])[CH:41]=[CH:42][C:28]=2[NH:27][C:26]1=O>ClCCCl>[CH3:21][O:22][C:23](=[O:46])[CH2:24][C@@H:25]1[N:31]=[C:30]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[C:29]2[CH:39]=[C:40]([O:43][CH3:44])[CH:41]=[CH:42][C:28]=2[NH:27][C:26]1=[S:2]

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]acetate

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
65 °C

Procedure

A suspension of P4S10 (85.8 g, 190 mmol) and Na2CO3 (20.5 g, 190 mmol) in 1,2-DCE (1.5 L) at RT was stirred for 1 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 Intermediate 5) (40 g, 107 mmol) was added. The resulting mixture was stirred at 65° C. for 4 h before being cooled and filtered. The solid was washed with DCM and the filtrate washed with sat. NaHCO3. The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound was precipitated from a DCM/i-Pr2O mixture and filtered. The filtrate was then concentrated and purified by flash chromatography (DCM/MeOH: 98/2) to afford another batch of product. The title compound was obtained combining the two fractions (30.2 g, 73%) as a yellow powder. LC/MS: m/z 389 [M(35Cl)+H]+, Rt 3.29 min.

Workup

  1. additionwas added
  2. temperaturebefore being cooled
  3. filtrationfiltered
  4. washThe solid was washed with DCM
  5. washthe filtrate washed with sat. NaHCO3
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe title compound was precipitated from a DCM/i-Pr2O mixture
  10. filtrationfiltered
  11. concentrationThe filtrate was then concentrated
  12. custompurified by flash chromatography (DCM/MeOH: 98/2)
  13. customto afford another batch of product

Sources & evidence

ORD record
ord-4f3f923fdb354641981c26f97768e553
Source dataset
uspto-grants-2015_05
Patent number
US09023842B2

Reaction notes

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