Sodium hydride → (3RS)-1-(benzothiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one

HRID 963457Notes

Reaction equation

HRID 963457 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[NH:14][C:13](=[O:21])[CH:12]([N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])[N:11]=1.Br[CH2:34][C:35]1[S:36][C:37]2[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=2[N:39]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.O.C(OCC)(=O)C.C(O)(=O)C>[S:36]1[C:37]2[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=2[N:39]=[C:35]1[CH2:34][N:14]1[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:10]([C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[F:3])=[N:11][CH:12]([N:22]2[C:23](=[O:32])[C:24]3=[CH:31][CH:30]=[CH:29][CH:28]=[C:25]3[C:26]2=[O:27])[C:13]1=[O:21]

Participants

9

Reactant 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 27762582-(Bromomethyl)-1,3-benzothiazoleHCID 19081136(3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one

Product 1

HCID 19081221(3RS)-1-(benzothiazol-2-yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride (0.11 g of a 60% dispersion in mineral oil) in N,N-dimethylformamide (20 ml) was added gradually (3RS)-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one (1.00 g) under nitrogen atmosphere at cooling in an ice-bath. The mixture was stirred under the same condition for 0.5 hour and at ambient temperature for 1 hour. The mixture was cooled in an ice-bath and a solution of 2-bromomethyl-benzothiazole (0.63 g) in N,N-dimethylformamide (5 ml) was added dropwise thereto. The mixture was stirred for 1 hour at the same temperature and at ambient temperature overnight. To the reaction mixture was added acetic acid (0.5 g) under cooling in an ice-bath. The resultant mixture was poured into a mixture of ethyl acetate (100 ml) and water (50 ml) under stirring. The mixture was adjusted to pH 7.5-8.0 with sodium bicarbonate. The organic layer was separated. The aqueous layer was extracted with ethyl acetate (50 ml). The combined organic layer was washed with a brine (50 ml), dried over magnesium sulfate, filtered and concentrated in vacuo to afford (3RS)-1-(benzothiazol-2 -yl)methyl-2,3-dihydro-5-(2-fluorophenyl)-3-phthalimido-1H-1,4-benzodiazepin-2-one. This product was allowed to use in a next reaction step without further purification.

Workup

  1. temperatureat cooling in an ice-bath
  2. temperatureThe mixture was cooled in an ice-bath
  3. stirringThe mixture was stirred for 1 hour at the same temperature and at ambient temperature overnight
  4. temperatureunder cooling in an ice-bath
  5. stirringunder stirring
  6. customThe organic layer was separated
  7. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
  8. washThe combined organic layer was washed with a brine (50 ml)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a2783376c63442c391ab18e6872b4b85
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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