(+-)-Quinacrine → 9-Aminoacridine

HRID 362191Notes

Reaction equation

HRID 362191 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-02395e615b4d4f6fab01ec9d084c4991
Source dataset
uspto-grants-1999_02
Patent number
US05869465

Reaction notes

Loading…