Clonazepam → 5-(2-chlorophenyl)-2-[bis(morpholino)phosphinyloxy]-7-nitro-3H-1,4-benzodiazepine

HRID 649265

Reaction equation

HRID 649265 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=[O:22])[CH2:10][N:9]=1.[H-].[Na+].[H-].[H][H].[O:28]1[CH2:33][CH2:32][N:31]([P:34](Cl)([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[O:35])[CH2:30][CH2:29]1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[N:12]=[C:11]([O:22][P:34]([N:36]2[CH2:37][CH2:38][O:39][CH2:40][CH2:41]2)([N:31]2[CH2:32][CH2:33][O:28][CH2:29][CH2:30]2)=[O:35])[CH2:10][N:9]=1

Participants

7

Reactant 5

HCID 2802ClonazepamHCID 24758Sodium hydrideHCID 166653HydrideHCID 12506606Bis(morpholino)phosphinyl chlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 201429915-(2-chlorophenyl)-2-[bis(morpholino)phosphinyloxy]-7-nitro-3H-1,4-benzodiazepine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4.74 g (15 mmoles) of 5-(2-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one in 80 ml of dry tetrahydrofuran at room temperature was added 875 mg of a 50% dispersion of sodium hydride in oil (18 mmoles of hydride). The mixtute was stirred at room temperature for 1 hr until hydrogen evolution stopped. Dimorpholinophosphinic chloride (7.5 g, 30 mmoles) was added and the resulting mixture was stirred at room temperature for 3 hrs. Solids (mixture of product and salt) were collected and partitioned between water and methylene chloride. The methylene chloride layer was dried and evaporated. Crystallization of the residue from methylene chloride ether gave colorless needles, mp 214°-216°.

Workup

  1. additionSolids (mixture of product and salt)
  2. customwere collected
  3. custompartitioned between water and methylene chloride
  4. dry with materialThe methylene chloride layer was dried
  5. customevaporated
  6. customCrystallization of the residue from methylene chloride ether
  7. customgave colorless needles, mp 214°-216°

Sources & evidence

ORD record
ord-455a76d780e64a069b13066b8c593c22
Source dataset
uspto-grants-1988_04
Patent number
US04739049

Linked notes

Loading…