Sodium Methoxide → Cladribine

HRID 2197388Notes

Reaction equation

HRID 2197388 reaction equation
C[O-].[Na+].[Cl:4][C:5]1[N:13]=[C:12]2[C:8]([N:9]=[CH:10][N:11]2[C@@H:14]2[O:28][C@H:27]([CH2:29][O:30]C(=O)C3C=CC(Cl)=CC=3)[C@@H:16]([O:17]C(=O)C3C=CC(Cl)=CC=3)[CH2:15]2)=[C:7]([NH:40][Si](C)(C)C)[N:6]=1>CO>[CH:10]1[N:11]([C@@H:14]2[O:28][C@H:27]([CH2:29][OH:30])[C@@H:16]([OH:17])[CH2:15]2)[C:12]2[C:8](=[C:7]([NH2:40])[N:6]=[C:5]([Cl:4])[N:13]=2)[N:9]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 532591302-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-beta-D-ribofurano syl]-purine

Product 1

HCID 20279CladribineYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
25 °C

Procedure

To a mixture of 25% sodium methoxide in MeOH (0.11 Kg, 0.5 mol, 0.1 eq.) and MeOH (14.8 Kg, 5 P) at about at 25° C. was added 2-chloro-6-trimethylsilylamino-9-[3,5-di-O-(4-chlorobenzoyl)-2-deoxy-β-D-ribofuranosyl]-purine (IVa) and non-silylated derivative 2-chloro-6-amino-9-[3,5-di-O-(4-chlorobenzoyl)-2′-deoxy-β-D-ribofuranosyl]-purine (IVb) (3.70 Kg, combined HPLC purity of >96.3%) and the mixture was agitated at about 25° C. for 2 hours. The solids were filtered, washed with MeOH (1.11 Kg, 0.4 P) and then dried in vacuo at 60° C. for 4 hours to give 1.43 Kg of a crude cladribine with 97.8% HPLC purity in ca. 87% yield.

Workup

  1. filtrationThe solids were filtered
  2. washwashed with MeOH (1.11 Kg, 0.4 P)
  3. customdried in vacuo at 60° C. for 4 hours

Sources & evidence

ORD record
ord-d6a00cb6082b4a53af1dbb96b0a675da
Source dataset
uspto-grants-2012_12
Patent number
US08338586B2

Reaction notes

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