Ethyl Acetate → (3RS)-3-amino-1-(benzo-thiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzo-diazepin-2-one

HRID 963458Notes

Reaction equation

HRID 963458 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:28])=[N:14][CH:13]([N:29]2C(=O)C3=CC=CC=C3C2=O)[C:12]1=[O:40].O.NN.C(OCC)(=O)C>C1COCC1>[NH2:29][CH:13]1[N:14]=[C:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:28])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N:11]([CH2:10][C:2]2[S:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[C:12]1=[O:40]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 19081221(3RS)-1-(benzothiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one

Product 1

HCID 19081252(3RS)-3-amino-1-(benzo-thiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzo-diazepin-2-oneYield 11.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of (3RS)-1-(benzothiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one (1.30 g) in THF (50 ml) was added dropwise hydrazine monohydrate (0.12 g) under stirring at ambient temperature. The mixture was stirred for 2 hours at the same temperature and refluxed under stirring for 2 hours. The reaction mixture was cooled in an ice-bath. The resultant precipitates were filtered off atad washed with THF (30 ml). The filtrate and washing were combined and concentrated in vacuo to afford a crude product. The product was dissolved into ethyl acetate (150 ml) and extracted with 1N-HCl aqueous solution (3×25 ml). The aqueous layer was alkalined with sodium bicarbonate and extracted with ethyl acetate (2×100 ml). The extracts were dried over magnesium sulfate and filtered off by filtration. The filtrate was concentrated in vacuo to afford (3RS)-3-amino-1-(benzo-thiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzo-diazepin-2-one as a colorless crystalline solid (110 mg). The compound was allowed to use in a next reaction step without further purification.

Workup

  1. stirringThe mixture was stirred for 2 hours at the same temperature
  2. temperaturerefluxed
  3. stirringunder stirring for 2 hours
  4. temperatureThe reaction mixture was cooled in an ice-bath
  5. customThe resultant precipitates
  6. filtrationwere filtered off
  7. washatad washed with THF (30 ml)
  8. washThe filtrate and washing
  9. concentrationconcentrated in vacuo
  10. customto afford a crude product
  11. extractionextracted with 1N-HCl aqueous solution (3×25 ml)
  12. extractionextracted with ethyl acetate (2×100 ml)
  13. dry with materialThe extracts were dried over magnesium sulfate
  14. filtrationfiltered off by filtration
  15. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-83f55a51ab984d41a3f461f0adbbc3dd
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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