Methane → 5,11-Dihydro-11-[4-(1-pyrrolidinyl)-but-2-ynyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

HRID 1084700Notes

Reaction equation

HRID 1084700 reaction equation
[CH2:1]([N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[C:8](=[O:15])[NH:7][C:6]2[CH:16]=[CH:17][CH:18]=[N:19][C:5]1=2)[C:2]#[CH:3].[CH2:20]=O.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.C>[Cu]Cl.O1CCOCC1>[N:22]1([CH2:20][C:3]#[C:2][CH2:1][N:4]2[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[NH:7][C:6]3[CH:16]=[CH:17][CH:18]=[N:19][C:5]2=3)[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 297MethaneHCID 712FormaldehydeHCID 31268PyrrolidineHCID 145520855,11-dihydro-11-(2-propynyl)-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

Product 1

HCID 145520865,11-Dihydro-11-[4-(1-pyrrolidinyl)-but-2-ynyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 312751,4-DioxaneSolvent

Procedure

The mixture of 8.5 g (0.034 mol) of 5,11-dihydro-11-(prop-2-ynyl)-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one, 50 ml of anhydrous dioxan, 1.08 g (0.036 mol) of paraformaldehyde, 2.77 g (0.039 mol) of pyrrolidine and 0.2 g of copper (I) chloride was refluxed for 1 hour with stirring and then, after cooling, evaporated down in a water jet vacuum. The residue was partitioned between water and ethylacetate, the ethylacetate solution obtained was mixed with 2 g of animal charcoal, dried over sodium sulphate, filtered and evaporated down. The residue was purified by column chromatography on silica gel using first ethyl acetate and then dichloromethane/cyclohexane/methanol/conc. ammonia 68/15/15/2 (v/v/v/v) as eluant. The crude product obtained after evaporation of the suitable eluates was recrystallised once more from ethylacetate. Yield: 1.6 g (14% of theory) of colourless crystals, m.p. 153° C.; RF 0.5 (Merck, ready-made TLC plates, silica gel 60 F-254; eluant: dichloromethane/cyclohexane/methanol/conc. ammonia 68/15/15/2 v/v/v/v).

Workup

  1. temperaturewas refluxed for 1 hour
  2. temperatureafter cooling
  3. customevaporated down in a water jet vacuum
  4. customThe residue was partitioned between water and ethylacetate
  5. customthe ethylacetate solution obtained
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated down
  9. customThe residue was purified by column chromatography on silica gel using first ethyl acetate

Sources & evidence

ORD record
ord-25ee1265146d4252b68fddb67155b27f
Source dataset
uspto-grants-1991_04
Patent number
US05006522

Reaction notes

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