(+-)-Quinacrine → 9-Aminoacridine

HRID 1598936Notes

Reaction equation

HRID 1598936 reaction equation
CCN(CCCC([NH:11][C:12]1[C:13]2[CH:14]=[CH:15][C:16](Cl)=[CH:17][C:18]=2[N:19]=[C:20]2[CH:25]=[CH:24][C:23](OC)=[CH:22][C:21]=12)C)CC.NCCCCN.ClC1C=C2C(=CC=1)C(Cl)=C1C(C=CC(OC)=C1)=N2.[OH-].[Na+]>C1(O)C=CC=CC=1>[CH:23]1[CH:24]=[CH:25][C:20]2[N:19]=[C:18]3[C:13]([CH:14]=[CH:15][CH:16]=[CH:17]3)=[C:12]([NH2:11])[C:21]=2[CH:22]=1

Participants

6

Reactant 4

HCID 237(+-)-QuinacrineHCID 1045PutrescineHCID 14798Sodium HydroxideHCID 665773,9-Dichloro-7-methoxyacridine

Product 1

HCID 70199-Aminoacridine

Reagents, catalysts & solvents 1

HCID 996PhenolSolvent

Procedure

A diamine side chain is first synthesized in a manner analogous to the side chain of quinacrine. Specifically, mono-phthaloyl protected 1,4-diaminobutane (27) is reacted with 6,9-dichloro-2-methoxyacridine (28) in phenol (J. Am. Chem. Soc. 66:1921-1924, 1944). The reaction mixture is then poured into an excess of 2N NaOH and extracted with ether. The ether extract is washed with 1M NaHCO3, then H2O, and dried over MgSO4. The crude product is recrystallized from H2O-alcohol. The phthaloyl protecting group is removed using anhydrous hydrazine in MeOH (Bioconjugate Chem. 2:435-440, 1991) to yield the aminoacridine, (29). Aminoacridine (29) is then conjugated with vitamin B12 monocarboxylic acid (2, 3, 4) to yield a cyanocobalamin-acridine conjugate (30).

Workup

  1. extractionextracted with ether
  2. extractionThe ether extract
  3. washis washed with 1M NaHCO3
  4. dry with materialH2O, and dried over MgSO4
  5. customThe crude product is recrystallized from H2O-alcohol
  6. customThe phthaloyl protecting group is removed

Sources & evidence

ORD record
ord-ed90b793102b4b8fbdfa824e89b405d2
Source dataset
uspto-grants-1998_04
Patent number
US05739287

Reaction notes

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