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

HRID 2264876Notes

Reaction equation

HRID 2264876 reaction equation
[Na].[CH2:2]([C:5]1[N:6]([C:10]2[N:18]=[CH:17][N:16]=[C:15]3[C:11]=2[NH:12][CH:13]=[N:14]3)[CH:7]=[CH:8][N:9]=1)[CH2:3][CH3:4].[C:19]1([CH3:45])[CH:24]=[CH:23][C:22]([C:25]([O:27][C@@H:28]2[C@@H:32]([CH2:33][O:34][C:35]([C:37]3[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=3)=[O:36])[O:31][C@H:30](Cl)[CH2:29]2)=[O:26])=[CH:21][CH:20]=1>CC#N.C1(C)C=CC=CC=1>[C:19]1([CH3:45])[CH:20]=[CH:21][C:22]([C:25]([O:27][C@@H:28]2[C@@H:32]([CH2:33][O:34][C:35]([C:37]3[CH:38]=[CH:39][C:40]([CH3:43])=[CH:41][CH:42]=3)=[O:36])[O:31][C@@H:30]([N:14]3[CH:13]=[N:12][C:11]4[C:15]3=[N:16][CH:17]=[N:18][C:10]=4[N:6]3[CH:7]=[CH:8][N:9]=[C:5]3[CH2:2][CH2:3][CH3:4])[CH2:29]2)=[O:26])=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 98571Hoffer's chlorosugarHCID 5360545SodiumHCID 116515276-(2-Propylimidazol-1-yl)purine

Product 1

HCID 160892149-[2-Deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purineYield 53%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

The sodium salt of 6-(2-propylimidazol-1-yl)purine (55 mg, 0.24 mmol) in dried CH3CN (5 mL) was treated with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (0.15 g, 0.39 mmol) in toluene (5 mL) by general method 1. The residue was chromatographed (25 g silica gel, MeOH/CH2Cl2, 1:12) to give the two diastereomers [quantitative, containing traces of α-anomer (α/β ˜1:34)]. Recrystallization (EtOAc) gave 9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purine (68.7 mg, 53%): mp 197-197.5° C.; UV (MeOH) max 242, 276 nm (∈ 31200, 12 500), min 223, 263 nm (∈ 16 400, 9700); 1H NMR (500 MHz, CDCl3) δ 8.80 (s, 1H), 8.41 (s, 1H), 8.28 (s, 1H), 8.00 (d, J=8.3 Hz, 2H), 7.89 (d, J=8.3 Hz, 2H), 7.31 (d, J=8.3 Hz, 2H), 7.21 (d, J=8.3 Hz, 2H), 7.12 (s, 1H) 6.65 (dd, J=6.2, 8.1 Hz, 1H), 5.85-5.87 (m, 1H), 4.68-4.83 (m, 3H), 3.30 (t, J=7.3 Hz, 2H), 3.17-3.23 (m, 1H), 2.91-2.95 (m, 1H), 2.47 (s, 3H), 2.39 (s, 3H), 1.85 (sext, J=7.5 Hz, 2H), 1.03 (t, J=7.3 Hz, 3H); NOE difference: irradiation at H1′ gave enhancement of the H4′ (small), H8 and H2′,2″ signals; 13C NMR (125 MHz, CDCl3) δ 166.4, 166.2, 153.1, 152.1, 151.0, 148.1, 144.9, 144.6, 142.4, 130.1, 129.8, 129.6, 129.5, 128.8, 126.8, 126.5, 124.6, 120.8, 85.5, 83.6, 75.2, 64.1, 38.3, 32.8, 22.0, 21.9, 21.5, 14.3; HRMS m/z 603.2347 (MNa+ [C32H32N6O5Na]=603.2332); Anal. Calcd for C32H32N6O5: C, 66.20; H, 5.56; N, 14.47. Found: C, 66.59; H, 5.67; N, 14.62.

Workup

  1. customThe residue was chromatographed (25 g silica gel, MeOH/CH2Cl2, 1:12)
  2. customto give
  3. additionthe two diastereomers [quantitative, containing traces of α-anomer (α/β ˜1:34)]
  4. customRecrystallization (EtOAc)

Sources & evidence

ORD record
ord-8904bb5272254090be93c8aa8619d670
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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