2-Aminobenzonitrile → 4-Aminoquinoline

HRID 392631

Reaction equation

HRID 392631 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C(O)(=O)C.N1[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[NH:17][CH:16]=1.[NH2:24][C:25]1C=CC=C[C:26]=1C#N>C1COCC1>[NH2:24][C:25]1[C:19]2[C:18](=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:17]=[CH:16][CH:26]=1

Participants

5

Reactant 3

HCID 729132-AminobenzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 67199695Benzimidazole acetate

Product 1

HCID 684764-Aminoquinoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

LiHMDS (3-4 eq) was added to the benzimidazole acetate (1.0 eq) in THF (at a constant temperature ranging from −78° C. to 0° C.). After 20 minutes, a solution of the 2-aminobenzonitrile (1.1 eq) in THF was then added. The resulting mixture was allowed to warm to room temperature, stirred for 1-3 hours and was then heated to approx. 40° C.-65° C.(1 hour to 12 hours). The mixture was cooled to 0° C. and quenched with NH4Cl (aq, saturated). The aqueous phase was extracted with Ch2Cl2 or EtOAc, and the organic extracts were collected, dried (Na2SO4), and filtered. Evaporation of the solvent under reduced pressure and purification of the residue by silica gel chromatography or HPLC provided the 4-amino quinoline products.

Workup

  1. customranging from −78° C. to 0° C.
  2. temperaturewas then heated to approx. 40° C.-65° C.(1 hour to 12 hours)
  3. temperatureThe mixture was cooled to 0° C.
  4. customquenched with NH4Cl (aq, saturated)
  5. extractionThe aqueous phase was extracted with Ch2Cl2 or EtOAc
  6. customthe organic extracts were collected
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customEvaporation of the solvent
  10. customunder reduced pressure and purification of the residue by silica gel chromatography or HPLC

Sources & evidence

ORD record
ord-cb4a92211ca7435d99b3046171b4a071
Source dataset
uspto-grants-2004_10
Patent number
US06800760B2

Linked notes

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