Potassium Carbonate → 2,6a,8,11-Tetraazabenzo[a]fluorene

HRID 921045Notes

Reaction equation

HRID 921045 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8](C(C)(C)C)=[N:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C([C:20]1[C:25](Br)=[C:24](I)[CH:23]=[CH:22][N:21]=1)(C)(C)C.FC(F)(F)C1C=C(I)C(Cl)=CN=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC1C=CC=CC=1C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:10]1[C:11]2[C:2]3[N:3]([CH:4]=[CH:5][C:6]=2[CH:7]=[CH:8][N:9]=1)[C:23]1[C:24](=[CH:25][CH:20]=[N:21][CH:22]=1)[N:1]=3

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 587173846-Tert-butyl-2,7-naphthyridin-1-amine2×HCID 674788695-Chloro-4-iodo-2-(trifluoromethyl)pyridineHCID 679953862-tert-Butyl-3-bromo-4-iodopyridine

Product 1

HCID 866802552,6a,8,11-Tetraazabenzo[a]fluorene

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7237O-XyleneSolvent

Procedure

A vigorously stirred mixture of 20.1 g (100 mmol) of 1-amino-6-tert-butyl-2,7-naphthyridine S41, 37.4 g (110 mmol) of 2-tert-butyl-3-bromo-4-iodopyridine (S27) or 27.9 g (110 mmol) of 2-trifluoromethyl-4-iodo-5-chloropyridine, 35.0 g (250 mmol) of potassium carbonate, 200 g of glass beads (diameter 3 mm), 2.6 g (10 mmol) of triphenylphosphine and 450 mg (2 mmol) of palladium(II) acetate in 500 ml of o-xylene is heated under reflux until the 1-amino-6-tert-butyl-2,7-naphthyridine has been consumed (typically 3-30 h). After cooling, the solid is filtered off via a silica-gel bed, rinsed with 1000 ml of THF, and the filtrate is evaporated to dryness. The residue is dissolved in 75 ml of ethyl acetate at the boiling temperature, and 250 ml of n-heptane are slowly added. After cooling, the solid which has crystallised out is filtered off with suction, washed twice with 50 ml of n-heptane each time and dried in vacuo. The solids obtained in this way are freed from low-boiling components and non-volatile secondary components by sublimation (p about 1×10−5 mbar, T about 170-200° C.). Purity according to 1H-NMR typically >99.5%.

Workup

  1. temperatureis heated
  2. customhas been consumed (typically 3-30 h)
  3. temperatureAfter cooling
  4. filtrationthe solid is filtered off via a silica-gel bed
  5. washrinsed with 1000 ml of THF
  6. customthe filtrate is evaporated to dryness
  7. dissolutionThe residue is dissolved in 75 ml of ethyl acetate at the boiling temperature, and 250 ml of n-heptane
  8. additionare slowly added
  9. temperatureAfter cooling
  10. customthe solid which has crystallised out
  11. filtrationis filtered off with suction
  12. washwashed twice with 50 ml of n-heptane each time
  13. customdried in vacuo
  14. customThe solids obtained in this way
  15. customare freed from low-boiling components and non-volatile secondary components by sublimation (p about 1×10−5 mbar, T about 170-200° C.)

Sources & evidence

ORD record
ord-2adaf0f840814af190edd460217d2871
Source dataset
uspto-grants-2016_03
Patent number
US09273080B2

Reaction notes

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