Hoffer's chlorosugar → 2-Chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(4,5-diphenylimidazol-1-yl)purine

HRID 2264877Notes

Reaction equation

HRID 2264877 reaction equation
[Na].[Cl:2][C:3]1[N:11]=[C:10]2[C:6]([NH:7][CH:8]=[N:9]2)=[C:5]([N:12]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:15]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:14]=[CH:13]2)[N:4]=1.[C:29]1([CH3:55])[CH:34]=[CH:33][C:32]([C:35]([O:37][C@@H:38]2[C@@H:42]([CH2:43][O:44][C:45]([C:47]3[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=3)=[O:46])[O:41][C@H:40](Cl)[CH2:39]2)=[O:36])=[CH:31][CH:30]=1>CC#N.C(Cl)Cl>[Cl:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@@H:40]2[O:41][C@H:42]([CH2:43][O:44][C:45]([C:47]3[CH:48]=[CH:49][C:50]([CH3:53])=[CH:51][CH:52]=3)=[O:46])[C@@H:38]([O:37][C:35]([C:32]3[CH:31]=[CH:30][C:29]([CH3:55])=[CH:34][CH:33]=3)=[O:36])[CH2:39]2)=[C:5]([N:12]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:15]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[N:14]=[CH:13]2)[N:4]=1

Participants

6

Reactant 3

HCID 98571Hoffer's chlorosugarHCID 5360545SodiumHCID 116536382-Chloro-6-(4,5-diphenylimidazol-1-yl)purine

Product 1

HCID 160892182-Chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(4,5-diphenylimidazol-1-yl)purine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The sodium salt of 2-chloro-6-(4,5-diphenylimidazol-1-yl)purine (94 mg, 0.25 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 no α-nucleoside by 1H NMR (500 MHz). Volatiles were evaporated in vacuo, and the residue was chromatographed (25 g silica gel, EtOAc/hexanes, 3:7→1:1) to give the β-anomer (quantitative). Recrystallization (EtOAc/hexanes) gave 2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]-6-(4,5-diphenylimidazol-1-yl)purine: UV (MeOH) max 240, 275 nm (∈ 53 400, 19 300), min 223, 270 nm (∈ 42 000, 19 100); 1H NMR (500 MHz, CDCl3) δ 8.97 (s, 1H), 8.25 (s, 1H), 7.97 (d, J=7.9 Hz, 2H), 7.86 (d, J=7.9 Hz, 2H), 7.55 (d, J=8.2 Hz, 2H), 7.19-7.40 (m, 13H), 6.56 (t, J=7.0 Hz, 1H), 5.77-5.78 (m, 1H), 4.76-4.79 (m, 1H), 4.65-4.69 (m, 2H), 2.92-2.96 (m, 2H), 2.45 (s, 3H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 166.06, 165.94, 154.03, 153.17, 147.13, 144.71, 144.45, 142.81, 140.38, 139.24, 133.50, 131.02, 129.85, 129.55, 129.37, 129.34, 128.25, 128.17, 127.47, 127.17, 126.41, 126.18, 124.00, 85.11, 83.52, 74.85, 63.84, 38.57, 21.78, 21.71; HRMS m/z 747.2100 (MNa+[C41H33ClN6O5Na]=747.2099).

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→1:1)
  4. customto give the β-anomer (quantitative)
  5. customRecrystallization (EtOAc/hexanes)

Sources & evidence

ORD record
ord-36d4e19f035949528b43967b283ca179
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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