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

HRID 2264880Notes

Reaction equation

HRID 2264880 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[CH2:17][CH2:18][CH3:19])[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.CO.C(Cl)Cl>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[CH2:17][CH2:18][CH3:19])[N:4]=1

Participants

7

Reactant 4

HCID 98571Hoffer's chlorosugarHCID 5360545SodiumHCID 115579952-Chloro-6-(2-propylimidazol-1-yl)purineHCID 21226129Dichloromethane methanol

Product 1

HCID 160880882-Chloro-9-[2-deoxy-3,5-di-o-(p-toluoyl)-beta-d-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purineYield 84.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

The sodium salt of 2-chloro-6-(2-propylimidazol-1-yl)purine (0.13 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 (0.30 g, 0.8 mmol) in CH2Cl2 (10 mL) by general method 2. No α-nucleoside was detected by 1H NMR. Column chromatography was performed twice (25 g silica gel, MeOH/CH2Cl2, 1:30, and EtOAc/hexanes, 1:1) to give 2-chloro-9-[2-deoxy-3,5-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl]-6-(2-propylimidazol-1-yl)purine (0.26 g, 83%), which was recrystallized (EtOAc) to give analytically pure material (0.17 g, 55%): mp 192-193° C.; UV (MeOH) max 220, 239, 287 nm (∈ 40 700, 38 300, 16 700), min 231, 265 nm (∈ 35 900, 10 300); 1H NMR (500 MHz, CDCl3) δ 8.52 (s, 1H), 8.27 (s, 1H), 8.00 (d, J=7.8 Hz, 211), 7.86 (d, J=7.8 Hz, 2H), 7.32 (d, J=7.8 Hz, 2H), 7.28 (d, J=7.8 Hz, 2H), 7.20 (s, 1H), 6.61 (t, J=7.1 Hz, 1H), 5.82-5.83 (m, 1H), 4.84-4.68 (m, 3H), 3.29 (t, J=7.8 Hz, 2H), 2.98-3.01 (m, 2H), 2.47 (s, 3H), 2.38 (s, 3H), 1.86 (sext, J=7.5 Hz, 2H), 1.07 (t, J=7.3 Hz, 3H); NOE difference: H1′ was irradiated, and enhancement of H4′ (small), H8 and H2′,2″ signals was observed; 13C NMR (125 MHz, CDCl3) δ 166.29, 166.23, 154.38, 153.42, 151.47, 148.18, 144.97, 144.65, 142.40, 130.12, 129.78, 129.61, 129.56, 129.20, 126.63, 126.44, 122.95, 120.57, 85.46, 83.82, 75.19, 64.12, 38.88, 33.12, 22.03, 21.91, 21.60, 14.25; HRMS m/z 637.1940 (MNa+[C32H31ClN6O5Na=637.1942]). Anal. Calcd for C32H31ClN6O5: C, 62.49; H, 5.08; N, 13.66. Found: C, 62.44; H, 5.18; N, 13.72.

Sources & evidence

ORD record
ord-f6f0a8249412413d9f1f3e76ed90b4af
Source dataset
uspto-grants-2010_12
Patent number
US07855285B2

Reaction notes

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