Triethylorthoaceate → 8-Chloro-6-(2-fluorophenyl)-3a,4-dihydro-1-methyl-3H-imidazo[1,5-a][1,4]benzodiazepine-5-oxide

HRID 355530Notes

Reaction equation

HRID 355530 reaction equation
[C:1](O)(=O)[C:2](O)=O.[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[NH:17][CH:16]([CH2:18][NH2:19])[CH2:15][N+:14]([O-:20])=[C:13]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[C:12]=2[CH:28]=1.C(C(CC)(CC)C([O-])([O-])[O-])C>C(#N)C>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[C:1]([CH3:2])=[N:19][CH2:18][CH:16]3[CH2:15][N+:14]([O-:20])=[C:13]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[C:12]=2[CH:28]=1

Participants

4

Reactant 2

HCID 21875354TriethylorthoaceateHCID 178510496HCID 178510496, compound2×

Product 1

HCID 118241068-Chloro-6-(2-fluorophenyl)-3a,4-dihydro-1-methyl-3H-imidazo[1,5-a][1,4]benzodiazepine-5-oxide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A slurry of 7-chloro-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-methanamine-4-oxide oxalate salt (VIII, EXAMPLE 6, 35 g, 85 mmol) and triethylorthoacetate (23.5 ml, 128 mmol) in acetonitrile (175 ml) is stirred at reflux for 2 hr during which time the 7-chloro-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-methanamine-4-oxide (VIII) dissolves and ethanol/acetonitrile (about 75 ml) is removed by distillation under ordinary pressure. TLC and HPLC analysis shows the reaction is complete. The temperature is adjusted to 40° and methyl t-butyl ether (175 ml) is added dropwise over about 1 hr. The resulting slurry is cooled to 5°, stirred 1 hr, the solids are collected and are washed with t-butyl ether. The product is dried in the vacuum oven at 35° to give the title compound as the oxalate salt, mp=178°-180°; TLC (methylene chloride/methanol/ammonium hydroxide, 90/10/1) Rf =0.28.

Workup

  1. dissolutiondissolves
  2. customethanol/acetonitrile (about 75 ml) is removed by distillation under ordinary pressure
  3. customis adjusted to 40°
  4. additionmethyl t-butyl ether (175 ml) is added dropwise over about 1 hr
  5. temperatureThe resulting slurry is cooled to 5°
  6. customthe solids are collected
  7. washare washed with t-butyl ether
  8. customThe product is dried in the vacuum oven at 35°

Sources & evidence

ORD record
ord-bc89a8ad53ff4743a73b745807be07a1
Source dataset
uspto-grants-1998_11
Patent number
US05831089

Reaction notes

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