Morpholine → 9-Bromo-6-(4-morpholinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

HRID 4017Notes

Reaction equation

HRID 4017 reaction equation
[Br:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]3[CH2:17][CH2:16][C:15]4[C:7]3=[C:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=O)[NH:10][C:4]=2[CH:3]=1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.[OH-].[Na+]>[Ti](Cl)(Cl)(Cl)Cl.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]3[CH2:17][CH2:16][C:15]4[C:7]3=[C:8]([CH:12]=[CH:13][CH:14]=4)[C:9]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[N:10][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 138232839-Bromo-1,2dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine-6-one

Product 1

HCID 138233059-Bromo-6-(4-morpholinyl)-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 7.88 g (0.0250 mole) of 9-bromo-1,2-dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6-one and 1200 ml of toluene was heated under nitrogen, with stirring, until a solution resulted. Then there was added 21.8 g (0.250 mole) of morpholine, followed by 14.2 g (0.075 mole) of titanium tetrachloride. The mixture was heated under reflux for three hours, cooled to room temperature and treated with 500 ml of 2N sodium hydroxide solution. After stirring vigorously for 15 minutes, the layers were separated. The aqueous phase was extracted with 250 ml of toluene. The toluene layers were combined, washed once with 2N sodium hydroxide solution, twice with water, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to 8.6 g (90%) of product. Recrystallization from a hot solution of dichloromethane (80 ml) to which methanol (80 ml) was added provided the analytical sample, mp 216°-218° C.

Workup

  1. temperaturewas heated under nitrogen
  2. customresulted
  3. temperatureThe mixture was heated
  4. temperatureunder reflux for three hours
  5. stirringAfter stirring vigorously for 15 minutes
  6. customthe layers were separated
  7. extractionThe aqueous phase was extracted with 250 ml of toluene
  8. washwashed once with 2N sodium hydroxide solution, twice with water
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo to 8.6 g (90%) of product
  12. customRecrystallization from a hot solution of dichloromethane (80 ml) to which methanol (80 ml)
  13. additionwas added
  14. customprovided the analytical sample, mp 216°-218° C.

Sources & evidence

ORD record
ord-89f7b1fe33fd41fd9d2f66dd79fef021
Source dataset
uspto-grants-1988_02
Patent number
US04723007

Reaction notes

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