Chloroform → (3RS)-3-amino-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-1H-1,4-benzodiazepin-2-one

HRID 963456Notes

Reaction equation

HRID 963456 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]3[O:28][C:27](=[O:29])[CH:26]=[CH:25][C:24]=3[CH:30]=2)[C:11](=[O:31])[CH:10]([N:32]2C(=O)C3=CC=CC=C3C2=O)[N:9]=1.O.NN.C(Cl)(Cl)Cl>C1COCC1>[NH2:32][CH:10]1[N:9]=[C:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[N:12]([CH2:19][C:20]2[CH:21]=[CH:22][C:23]3[O:28][C:27](=[O:29])[CH:26]=[CH:25][C:24]=3[CH:30]=2)[C:11]1=[O:31]

Participants

5

Reactant 3

HCID 6212ChloroformHCID 24654Hydrazine hydrate (1:1)HCID 19081262(3RS)-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-3-phthalimido-1H-1,4-benzodiazepin-2-one

Product 1

HCID 19081358(3RS)-3-amino-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-1H-1,4-benzodiazepin-2-oneYield 30.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of (3RS)-2,3-dihydro-5-(2-flurophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-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 and washed with THF. The filtrate and washing were combined and concentrated in vacuo to afford a residue. The residue was dissolved into chloroform (100 ml) and extracted with 1N-HCl aqueous solution (2×25 ml). The aqueous layer was alkalined with sodium bicarbonate, extracted with chloroform (2×100 ml), dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to afford a crude product. The crude product was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate to afford (3RS)-3-amino-2,3-dihydro-5-(2-fluorophenyl)-1-(2-oxo-2H-1-benzopyran-6-yl)methyl-1H-1,4-benzodiazepin-2-one as a colorless crystalline solid (0.30 g).

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. washwashed with THF
  8. washThe filtrate and washing
  9. concentrationconcentrated in vacuo
  10. customto afford a residue
  11. extractionextracted with 1N-HCl aqueous solution (2×25 ml)
  12. extractionextracted with chloroform (2×100 ml)
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated in vacuo
  16. customto afford a crude product
  17. customThe crude product was purified by column chromatography on silica gel with an eluent of a mixture of chloroform and ethyl acetate

Sources & evidence

ORD record
ord-b52c61fb4a294ad9a1d56af5338c110c
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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