Ammonia methanol → Cladribine

HRID 2264883Notes

Reaction equation

HRID 2264883 reaction equation
[I-].C(N1C=C[N+:11]([C:14]2[N:22]=[C:21]([Cl:23])[N:20]=[C:19]3[C:15]=2[N:16]=[CH:17][N:18]3[C@@H:24]2[O:38][C@H:37]([CH2:39][O:40]C(C3C=CC(C)=CC=3)=O)[C@@H:26]([O:27]C(C3C=CC(C)=CC=3)=O)[CH2:25]2)=C1CCC)C1C=CC=CC=1.N.CO>O.CO>[NH2:11][C:14]1[N:22]=[C:21]([Cl:23])[N:20]=[C:19]2[C:15]=1[N:16]=[CH:17][N:18]2[C@@H:24]1[O:38][C@H:37]([CH2:39][OH:40])[C@@H:26]([OH:27])[CH2:25]1

Participants

4

Reactant 2

HCID 21705897Ammonia methanolHCID 178439997HCID 178439997, compound

Product 1

HCID 20279CladribineYield 108.9%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

Treatment of 3-benzyl-1-{2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]purin-6-yl}-2-propylimidazolium iodide (0.83 g, crude) with NH3/MeOH (26%, 50 mL) at 60° C. followed by ion exchange chromatography (Dowex 1×2 [OH−], H2O/MeOH) by method 3 gave cladribine (0.31 g, quantitative). Recrystallization from EtOH gave a white solid (0.153 g, 54%), and the residue from the mother liquor was recrystallized from H2O to give a second crop (0.015 g, 59% total): mp>300° C.; UV (MeOH) max 212, 265 nm (∈ 24 000, 14 600), min 229 nm (∈ 2000); 1H NMR (500 MHz, DMSO-d6) δ 8.36 (s, 1H), 7.83 (br, 2H), 6.26 (t, J=6.7 Hz, 1H), 5.32 (d, J=4.3 Hz, 1H), 4.97 (t, J=5.5 Hz, 1H), 4.38 (s, 1H), 3.85 (s, 1H), 3.57-3.61 (m, 1H), 3.48-3.53 (m, 1H), 2.62-2.67 (m, 1H), 2.25-2.29 (m, 1H); 13C NMR (125 MHz, DMSO-d6) δ 157.5, 153.6, 150.8, 140.5, 118.8, 88.6, 84.2, 71.4, 62.3, 38.0; HRMS m/z 285.0615 (M+ [C10H12ClN5O3]=285.0629). Anal. Calcd for C10H12ClN5O3: C, 42.04; H, 4.23; N, 24.51. Found: C, 41.87; H, 4.50; N, 24.39.

Workup

  1. customat 60° C.

Sources & evidence

ORD record
ord-a812c18a1eac475d9ffcd1ba355f3b6e
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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