Benzaldehyde → 11-Cyclopropyl-5,11-dihydro-4-phenacyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

HRID 53554

Reaction equation

HRID 53554 reaction equation
[CH:1]1([N:4]2[C:10]3[N:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[NH:7][C:6]3[C:16]([CH3:20])=[CH:17][CH:18]=[N:19][C:5]2=3)[CH2:3][CH2:2]1.[H-].[Na+].C([N-]C(C)C)(C)C.[Li+].[CH:31](=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O1CCCC1>[CH:1]1([N:4]2[C:10]3[N:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[NH:7][C:6]3[C:16]([CH2:20][C:31]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:38])=[CH:17][CH:18]=[N:19][C:5]2=3)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 240BenzaldehydeHCID 4463NevirapineHCID 24758Sodium hydrideHCID 2724682Lithium diisopropylamide

Product 1

HCID 1996007811-Cyclopropyl-5,11-dihydro-4-phenacyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-oneYield 7.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (1.0 g) in tetrahydrofuran (25 m L) was added NaH (80% in oil, 0.12 g). The mixture was stirred at room temperature for 30 min. and then cooled to -78° C. Lithium diisopropylamide (1.5 M in cyclohexane, 6.6 mL) was added and the mixture was stirred for an additional 45 min. Benzaldehyde (0.53 g) was added, the mixture was stirred at -65° C. for 1 hour and then allowed to warm to room temperature. The reaction was quenched with water and the volatile materials were removed under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, dried, filtered, and evaporated. The residue was chromatographed over silica gel with 40% ethyl acetate/hexane, and then purified by preparative layer chromatography to give 0.1 g of the title compound, m.p. 195°-197° C.

Workup

  1. temperaturecooled to -78° C
  2. stirringthe mixture was stirred for an additional 45 min
  3. stirringthe mixture was stirred at -65° C. for 1 hour
  4. temperatureto warm to room temperature
  5. customThe reaction was quenched with water
  6. customthe volatile materials were removed under reduced pressure
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. washwashed with water
  9. customdried
  10. filtrationfiltered
  11. customevaporated
  12. customThe residue was chromatographed over silica gel with 40% ethyl acetate/hexane
  13. custompurified by preparative layer chromatography

Sources & evidence

ORD record
ord-8a9ae86ae091467eb912607ba19743bd
Source dataset
uspto-grants-1997_04
Patent number
US05620974

Linked notes

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