Sodium Iodide → AF-DX-384

HRID 2351452Notes

Reaction equation

HRID 2351452 reaction equation
Br[CH2:2][CH2:3][NH:4][C:5]([N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11](=[O:18])[NH:10][C:9]2[CH:19]=[CH:20][CH:21]=[N:22][C:8]1=2)=[O:6].[CH2:23]([N:26]([CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][NH:32]1)[CH2:27][CH2:28][CH3:29])[CH2:24][CH3:25].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:23]([N:26]([CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][N:32]1[CH2:2][CH2:3][NH:4][C:5]([N:7]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[C:11](=[O:18])[NH:10][C:9]2[CH:19]=[CH:20][CH:21]=[N:22][C:8]1=2)=[O:6])[CH2:27][CH2:28][CH3:29])[CH2:24][CH3:25]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 10798040N-(Piperidin-2-ylmethyl)-N-propylpropan-1-amineHCID 1984600611-[[[2-bromo-ethyl]amino]carbonyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

Product 1

HCID 119357AF-DX-384

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

The darkened mixture of 1.806 g (0.005 mol) of 11-[[[2-bromo-ethyl]amino]carbonyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one, 0.992 g (0.005 mol) of 2-[(dipropylamino)-methyl]piperidine, 20 ml of anhydrous acetonitrile and 0.75 g (0.005 mol) of sodium iodide was refluxed for 4 hours with stirring under a nitrogen atmosphere. The mixture was left to cool, 50 ml of 10% aqueous potassium carbonate solution were added and the organic phase was separated off. The aqueous phase was extracted five times in all, with 10 ml aliquots of dichloromethane. The combined organic extracts were dried over sodium sulphate with the addition of animal charcoal and evaporated down in vacuo. The residue was purified by column chromatography on silica gel (30-60 microns) and using dichloromethane/cyclohexane/methanol/conc. ammonia 68/15/15/1 (v/v/v/v) as eluant. The corresponding eluates were evaporated down, the residue was recrystallised once from acetonitrile and dried in a vacuum dryer at 50° C. until a constant weight was obtained. 0.7 g (29% of theory) of colourless crystals were obtained, m.p. 163°-164° C., which were identical according to their mixed melting point, thin layer chromatogram and IR spectrum, to a preparation prepared according to Example 29.

Workup

  1. temperaturewas refluxed for 4 hours
  2. waitThe mixture was left
  3. temperatureto cool
  4. customthe organic phase was separated off
  5. extractionThe aqueous phase was extracted five times in all, with 10 ml aliquots of dichloromethane
  6. dry with materialThe combined organic extracts were dried over sodium sulphate with the addition of animal charcoal
  7. customevaporated down in vacuo
  8. customThe residue was purified by column chromatography on silica gel (30-60 microns)
  9. customThe corresponding eluates were evaporated down
  10. customthe residue was recrystallised once from acetonitrile
  11. customdried in a vacuum dryer at 50° C. until a constant weight
  12. customwas obtained
  13. custom0.7 g (29% of theory) of colourless crystals were obtained
  14. additionmixed melting point, thin layer chromatogram and IR spectrum
  15. customto a preparation prepared

Sources & evidence

ORD record
ord-7515d24aa94d4652bc7bc491877e11b5
Source dataset
uspto-grants-1989_10
Patent number
US04873236

Reaction notes

Loading…