HCID 16089217, compound → Cladribine

HRID 2264884Notes

Reaction equation

HRID 2264884 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:25][C@H:24]([CH2:26][O:27]C(C3C=CC(C)=CC=3)=O)[C@@H:13]([O:14]C(C3C=CC(C)=CC=3)=O)[CH2:12]2)=[C:4]([N:37]2C=CN=C2CCCCC)[N:3]=1>N>[NH2:37][C:4]1[N:3]=[C:2]([Cl:1])[N:10]=[C:9]2[C:5]=1[N:6]=[CH:7][N:8]2[C@@H:11]1[O:25][C@H:24]([CH2:26][OH:27])[C@@H:13]([OH:14])[CH2:12]1

Participants

3

Reactant 1

HCID 16089217HCID 16089217, compound

Product 1

HCID 20279Cladribine

Reagents, catalysts & solvents 1

HCID 222AmmoniaSolvent

Procedure

A solution of 2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]-6-(2-pentylimidazol-1-yl)purine (0.35 g, 0.55 mmol) in methanolic ammonia (14%) was stirred at 80° C. for 13 h. Volatiles were evaporated, and the oily residue was extracted with CH2Cl2 (10 mL) to remove lipophilic by-products. The semi-solid residue was dissolved in acetone (with additions of small amounts of MeOH—if necessary), volatiles were evaporated, and the semi-solid was allowed to crystallize (˜1 h). This material was extracted with CH2Cl2 (10 mL) and dried. The resulting 2-chloro-2′-deoxyadenosine (white powder; 113 mg, 70%) was pure by 1H NMR analysis. Additional amounts of cladribine (˜24 mg, 15%; containing traces of the α-anomer) were recovered from the concentrated extracts by chromatography (EtOAc→EtOAc/MeOH, 10:1) followed by a similar extraction sequence.

Workup

  1. customVolatiles were evaporated
  2. extractionthe oily residue was extracted with CH2Cl2 (10 mL)
  3. customto remove lipophilic by-products
  4. dissolutionThe semi-solid residue was dissolved in acetone (with additions of small amounts of MeOH—if necessary)
  5. customvolatiles were evaporated
  6. customto crystallize (˜1 h)
  7. extractionThis material was extracted with CH2Cl2 (10 mL)
  8. customdried
  9. customcontaining traces of the α-anomer) were recovered from the concentrated extracts by chromatography (EtOAc→EtOAc/MeOH, 10:1)

Sources & evidence

ORD record
ord-46f14745b5a348259a3a6b8b2ed81a83
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

Loading…