Sodium Iodide → (3RS)-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one

HRID 963469Notes

Reaction equation

HRID 963469 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][CH:11]1[N:17]=[C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[F:24])[C:15]2[CH:25]=[CH:26][CH:27]=[CH:28][C:14]=2[NH:13][C:12]1=[O:29])=[O:9])([CH3:6])([CH3:5])[CH3:4].[I-].[Na+].Cl[CH2:33][C:34]([N:36]1[CH2:44][CH:43]2[CH2:45][CH:39]3[CH2:40][CH:41]([CH2:46][CH:37]1[CH2:38]3)[CH2:42]2)=[O:35]>CN(C)C=O>[CH:37]12[CH2:46][CH:41]3[CH2:40][CH:39]([CH2:45][CH:43]([CH2:42]3)[CH2:44][N:36]1[C:34]([CH2:33][N:13]1[C:14]3[CH:28]=[CH:27][CH:26]=[CH:25][C:15]=3[C:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])=[N:17][CH:11]([NH:10][C:8]([O:7][C:3]([CH3:6])([CH3:4])[CH3:5])=[O:9])[C:12]1=[O:29])=[O:35])[CH2:38]2

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 19081122(3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-oneHCID 86752745N-chloromethylcarbonyl-2-azatricyclo-[4.3.1.14,8]undecane

Product 1

HCID 67688125(3RS)-1-[(2-azatricyclo[4.3.1.14,8]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-oneYield 120.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a suspension of sodium hydride (0.035 g of a 60% dispersion in mineral oil) in dry N,N-dimethylformamide (5 ml) was added dropwise a solution of (3RS)-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.293 g) in dry N,N-dimethylformamide (2 ml) under stirring at cooling in an ice-bath. After completion of the addition, the mixture was allowed to stand to room temperature and stirred for 2 hours. To the the mixture was added sodium iodide (0.129 g) and followed dropwise a solution of N-chloromethylcarbonyl-2-azatricyclo-[4.3.1.14,8 ]undecane (0.215 g) in dry N,N-dimethylformamide (2 ml) under stirring at cooing in an ice-bath for 1 hour and then at room temperature overnight. The reaction mixture was concentrated in vacuo. The residue was treated with ethyl acetate and water. The organic layer was washed with water and dried over sodium sulfate. Removal of the solvent gave (3RS)-1-[(2-azatricyclo[4.3.1.14,8 ]undec-2-yl)carbonylmethyl]-3-tert-butoxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepin-2-one (0.537 g), which was used in a following reaction step without further purification.

Workup

  1. temperatureat cooling in an ice-bath
  2. additionAfter completion of the addition
  3. customto stand to room temperature
  4. stirringstirred for 2 hours
  5. stirringunder stirring
  6. customat room temperature
  7. customovernight
  8. concentrationThe reaction mixture was concentrated in vacuo
  9. additionThe residue was treated with ethyl acetate and water
  10. washThe organic layer was washed with water
  11. dry with materialdried over sodium sulfate
  12. customRemoval of the solvent

Sources & evidence

ORD record
ord-d74e1b54a58d423c9c303dbf423343b6
Source dataset
uspto-grants-1998_06
Patent number
US05763437

Reaction notes

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