2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-beta-D-ribofurano syl]-purine → Cladribine

HRID 2197387Notes

Reaction equation

HRID 2197387 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(=O)C3C=CC(Cl)=CC=3)[C@@H:13]([O:14]C(=O)C3C=CC(Cl)=CC=3)[CH2:12]2)=[C:4]([NH:37][Si](C)(C)C)[N:3]=1.CO[Na].CO>CO>[CH:7]1[N:8]([C@@H:11]2[O:25][C@H:24]([CH2:26][OH:27])[C@@H:13]([OH:14])[CH2:12]2)[C:9]2[C:5](=[C:4]([NH2:37])[N:3]=[C:2]([Cl:1])[N:10]=2)[N:6]=1

Participants

4

Reactant 2

HCID 532591302-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-beta-D-ribofurano syl]-purineHCID 178501943HCID 178501943, compound

Product 1

HCID 20279CladribineYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To the above prepared mixture of 2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-β-D-ribofuranosyl]-purine (IVa) and 2-chloro-6-amino-9-[3,5-di-O-(4-chlorobenzoyl)-2′-deoxy-β-D-ribofuranosyl]-purine (IVb) (179 g, >95.4% HPLC purity) in MeOH (895 mL, 5 P) was added 29% MeONa/MeOH solution (5.25 g, 0.1 eq.) at 20-30° C. The mixture was stirred at 20-30° C. for 6 hours, the solid was filtered, washed with MeOH (60 mL, 0.34 P) and then dried in vacuo at 50° C. for 6 hour to give 72 g white to off-white crude cladribine with 98.9% HPLC purity in ca. 93% yield.

Workup

  1. filtrationthe solid was filtered
  2. washwashed with MeOH (60 mL, 0.34 P)
  3. customdried in vacuo at 50° C. for 6 hour

Sources & evidence

ORD record
ord-d00d24043a1648f79b58cced30efb796
Source dataset
uspto-grants-2012_12
Patent number
US08338586B2

Reaction notes

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