Acetyl chloride → Methyl [(3S)-2-[2-acetylhydrazino]-5-(4-chlorophenyl)-7-(methyloxy)-3H-1,4-benzodiazepin-3-yl]acetate

HRID 570173Notes

Reaction equation

HRID 570173 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][C@@H:5]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:8]=2[NH:7][C:6]1=S.O.[NH2:28][NH2:29].CCN(CC)CC.[C:37](Cl)(=[O:39])[CH3:38]>C1COCC1>[CH3:1][O:2][C:3](=[O:26])[CH2:4][C@@H:5]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[CH:19]=[C:20]([O:23][CH3:24])[CH:21]=[CH:22][C:8]=2[N:7]=[C:6]1[NH:28][NH:29][C:37](=[O:39])[CH3:38]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 57465560Methyl [(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-thioxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetate

Product 1

HCID 57465559Methyl [(3S)-2-[2-acetylhydrazino]-5-(4-chlorophenyl)-7-(methyloxy)-3H-1,4-benzodiazepin-3-yl]acetateYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of Methyl[(3S)-5-(4-chlorophenyl)-7-(methyloxy)-2-thioxo-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]acetate (for a preparation see Reference compound E (9.0 g, 23.2 mmol) in THF (300 mL) at 0° C. was added hydrazine monohydrate (3.4 mL, 69.6 mmol) dropwise. The reaction mixture was stirred for 5 h between 5° C. and 15° C. before being cooled at 0° C. Et3N (9.7 mL, 69.6 mmol) was then added slowly and acetyl chloride (7.95 mL, 69.6 mmol) was added dropwise. The mixture was then allowed to warm to room temperature for 16 h before being concentrated under reduced pressure. The crude product was dissolved in DCM and washed with water. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give the crude title compound (9.7 g, 98% yield) which was used without further purification. Rf=0.49 (DCM/MeOH: 90/10).

Workup

  1. customat 0° C.
  2. temperatureto warm to room temperature for 16 h
  3. concentrationbefore being concentrated under reduced pressure
  4. dissolutionThe crude product was dissolved in DCM
  5. washwashed with water
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4f8b8560ae6d4c9c82ffa327786b955f
Source dataset
uspto-grants-2015_05
Patent number
US09023842B2

Reaction notes

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