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

HRID 2264879Notes

Reaction equation

HRID 2264879 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[CH:16]=[CH:15][N:14]=[C:13]2[CH:17]([CH3:19])[CH3:18])[N:4]=1.[C:20]1([CH3:46])[CH:25]=[CH:24][C:23]([C:26]([O:28][C@@H:29]2[C@@H:33]([CH2:34][O:35][C:36]([C:38]3[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=3)=[O:37])[O:32][C@H:31](Cl)[CH2:30]2)=[O:27])=[CH:22][CH:21]=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:31]2[O:32][C@H:33]([CH2:34][O:35][C:36]([C:38]3[CH:39]=[CH:40][C:41]([CH3:44])=[CH:42][CH:43]=3)=[O:37])[C@@H:29]([O:28][C:26]([C:23]3[CH:22]=[CH:21][C:20]([CH3:46])=[CH:25][CH:24]=3)=[O:27])[CH2:30]2)=[C:5]([N:12]2[CH:16]=[CH:15][N:14]=[C:13]2[CH:17]([CH3:19])[CH3:18])[N:4]=1

Participants

6

Reactant 3

HCID 98571Hoffer's chlorosugarHCID 5360545SodiumHCID 866227772-Chloro-6-(2-isopropylimidazol-1-yl)purine

Product 1

HCID 160892082-Chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(2-isopropylimidazol-1-yl)purine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The sodium salt of 2-chloro-6-(2-isopropylimidazol-1-yl)purine (0.132 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 for 1 h (reaction complete, TLC). Sampling of the reaction mixture at the end of the reaction time showed no α-nucleoside by 1H NMR (500 MHz). The residue was chromatographed (25 g silica gel, EtOAc/hexanes˜1:1) to give 2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]-6-(2-isopropylimidazol-1-yl)purine (quantitative). Recrystallization (EtOAc) gave the compound (0.22 g, 70%): UV (MeOH) max 223, 241, 285 nm (∈ 32 100, 35 400, 14 800), min 230, 265 nm (∈ 30 300, 9200); 1H NMR (500 MHz, CDCl3) δ 8.42 (d, J=1.0 Hz, 1H), 8.26 (s, 1H), 7.99 (d, J=7.8 Hz, 2H), 7.85 (d, J=8.3 Hz, 2H), 7.30 (d, J=7.8 Hz, 2H), 7.20 (d, J=8.8 Hz, 2H), 7.11 (d, J=1.0 Hz, 1H), 6.60 (t, J=6.8 Hz, 1H), 5.81 (br s, 1H), 4.78-4.83 (m, 1H), 4.67-4.71 (m, 2H), 4.08 (sept, J=6.8 Hz, 1H), 2.97-3.01 (m, 2H), 2.46 (s, 3H), 2.37 (s, 3H), 1.43 (d, J=6.8 Hz, 3H), 1.41 (d, J=6.8 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 166.05, 165.99, 156.18, 154.20, 153.21, 148.15, 144.72, 144.40, 142.25, 129.88, 129.55, 129.36, 129.33, 128.82, 126.44, 126.26, 123.00, 120.38, 85.23, 83.59, 74.93, 63.87, 38.63, 28.81, 21.78, 21.61; HRMS 77/z 637.1931 (MNa+[C32H31ClN6O5Na=637.1942]).

Workup

  1. custom(reaction complete, TLC)
  2. aliquotSampling of the reaction mixture at the end of the reaction time
  3. customThe residue was chromatographed (25 g silica gel, EtOAc/hexanes˜1:1)

Sources & evidence

ORD record
ord-e08079208202418e9e25d1967ce2c0d2
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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