Hoffer's chlorosugar → 6-(2-Butylimidazol-1-yl)-2-chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]purine

HRID 2264878Notes

Reaction equation

HRID 2264878 reaction equation
[Na].[CH2:2]([C:6]1[N:7]([C:11]2[N:19]=[C:18]([Cl:20])[N:17]=[C:16]3[C:12]=2[NH:13][CH:14]=[N:15]3)[CH:8]=[CH:9][N:10]=1)[CH2:3][CH2:4][CH3:5].[C:21]1([CH3:47])[CH:26]=[CH:25][C:24]([C:27]([O:29][C@@H:30]2[C@@H:34]([CH2:35][O:36][C:37]([C:39]3[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=3)=[O:38])[O:33][C@H:32](Cl)[CH2:31]2)=[O:28])=[CH:23][CH:22]=1>CC#N.C(Cl)Cl>[CH2:2]([C:6]1[N:7]([C:11]2[N:19]=[C:18]([Cl:20])[N:17]=[C:16]3[C:12]=2[N:13]=[CH:14][N:15]3[C@@H:32]2[O:33][C@H:34]([CH2:35][O:36][C:37]([C:39]3[CH:40]=[CH:41][C:42]([CH3:45])=[CH:43][CH:44]=3)=[O:38])[C@@H:30]([O:29][C:27]([C:24]3[CH:23]=[CH:22][C:21]([CH3:47])=[CH:26][CH:25]=3)=[O:28])[CH2:31]2)[CH:8]=[CH:9][N:10]=1)[CH2:3][CH2:4][CH3:5]

Participants

6

Reactant 3

HCID 98571Hoffer's chlorosugarHCID 5360545SodiumHCID 115799846-(2-Butylimidazol-1-yl)-2-chloropurine

Product 1

HCID 160892096-(2-Butylimidazol-1-yl)-2-chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]purine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The sodium salt of 6-(2-butylimidazol-1-yl)-2-chloropurine (0.139 g, 0.5 mmol) in dried CH3CN (10 mL) was treated with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (0.334 g, 0.86 mmol) in CH2Cl2 (10 mL) by general method 2. Sampling of the reaction mixture showed traces of α-nucleoside by 1H NMR (500 MHz) (1:24). Volatiles were evaporated in vacuo, and the residue was chromatographed (25 g silica gel, EtOAc/hexanes, 3:7→EtOAc) to give the β-anomer (274 mg, 86%) with traces of the α-anomer. Recrystallization (EtOAc/hexanes) gave 6-(2-butylimidazol-1-yl)-2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]purine: UV (MeOH) max 223, 241, 287 nm (∈ 29 900, 33 400, 13 200), min 230, 265 nm (∈ 28 100, 7500); 1H NMR (500 MHz, CDCl3) δ 8.51 (s, 1H), 8.26 (s, 1H), 7.98 (d, J=8.0 Hz, 2H), 7.84 (d, J=8.0 Hz, 2H), 7.30 (d, J=8.0 Hz, 2H), 7.19 (d, J=8.0 Hz, 2H), 7.09 (s, 1H), 6.60 (t, J=6.9 Hz, 1H), 5.80 (br s, 1H), 4.78-4.81 (m, 1H), 4.66-4.70 (m, 2H), 3.31 (t, J=7.8 Hz, 2H), 2.97-3.00 (m, 2H), 2.46 (s, 3H), 2.37 (s, 3H), 1.80 (quint, J=7.4 Hz, 2H), 1.50 (sext, J=7.4 Hz, 2H), 0.97 (t, J=7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 166.05, 165.98, 154.13, 153.17, 151.43, 147.92, 144.71, 144.39, 142.18, 129.87, 129.53, 129.35, 129.31, 128.91, 126.38, 126.20, 122.70, 120.33, 85.20, 83.57, 74.94, 63.87, 38.61, 30.70, 30.07, 22.64, 21.79, 21.66, 13.91; HRMS 771/z 629.2270 (MH+[C33H34ClN6O5=629.2279]).

Workup

  1. aliquotSampling of the reaction mixture
  2. customVolatiles were evaporated in vacuo
  3. customthe residue was chromatographed (25 g silica gel, EtOAc/hexanes, 3:7→EtOAc)
  4. customto give the β-anomer (274 mg, 86%) with traces of the α-anomer
  5. customRecrystallization (EtOAc/hexanes)

Sources & evidence

ORD record
ord-ccf747845f39436ea7c3eadb7cc47ce1
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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