Sodium Methoxide → 5-Aza-2'-deoxycytidine

HRID 2043793Notes

Reaction equation

HRID 2043793 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]([C@@H:8]2[O:22][C@H:21]([CH2:23][O:24]C(=O)C3C=CC(Cl)=CC=3)[C@@H:10]([O:11]C(=O)C3C=CC(Cl)=CC=3)[CH2:9]2)[C:4](=[O:34])[N:3]=1.NC1N=CN([C@H]2O[C@H](COC(=O)C3C=CC(Cl)=CC=3)[C@@H](OC(=O)C3C=CC(Cl)=CC=3)C2)C(=O)N=1.C[O-].[Na+]>CO>[CH2:9]1[C@H:8]([N:5]2[C:4](=[O:34])[N:3]=[C:2]([NH2:1])[N:7]=[CH:6]2)[O:22][C@H:21]([CH2:23][OH:24])[C@H:10]1[OH:11]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 452568534-Amino-1-[3,5-bis-O-(4-chlorobenzoyl)-2-deoxy-beta-D-erythro-pentofuranosyl]-1,3,5-triazin-2(1H)-oneHCID 675340374-Amino-1-(3,5-bis-O-(4-chlorobenzoyl)-2-deoxy-alpha-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one

Product 1

HCID 4516685-Aza-2'-deoxycytidineYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A mixture of 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-β-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one in about 50% HPLC purity and 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-α-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one (6.15 Kg, 12.17 mol) and methanol (21.4 Kg) were charged into a suitable reactor at about 25° C. 30% Sodium methoxide in methanol solution (0.61 Kg) was added to the mixture solution and then stirred for 5 hours. The solids were filtered, washed with methanol (3.3 Kg) and dried at 50° C. for 14 hours to obtain 0.927 Kg (4.11 mol) crude decitabine in 97.1% HPLC purity (about 67% yield based on 4-amino-1-[3,5-di-O-(4-chloro-benzoyl)-2-deoxy-β-D-ribofuranosyl]-1H-[1,3,5]triazin-2-one (compound Ib)).

Workup

  1. additionwere charged into a suitable reactor at about 25° C
  2. filtrationThe solids were filtered
  3. washwashed with methanol (3.3 Kg)
  4. customdried at 50° C. for 14 hours

Sources & evidence

ORD record
ord-dae8519b40a5496e8ebcdd2b77e48abb
Source dataset
uspto-grants-2013_11
Patent number
US08586729B2

Reaction notes

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