(+-)-Quinacrine → 9-Aminoacridine

HRID 2287328Notes

Reaction equation

HRID 2287328 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 2 N NaOH and extracted with ether. The ether extract is washed with 1 M 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 1 M 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-4d157082256a43be92f5ac3fbf67e205
Source dataset
uspto-grants-2000_07
Patent number
US06083926

Reaction notes

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