2-Iodoadenosine → 2-(Trifluoromethyl)adenosine

HRID 2050602Notes

Reaction equation

[Br-].[F:2][C:3]([Zn+])([F:5])[F:4].I[C:8]1[N:9]=[C:10]([NH2:26])[C:11]2[N:12]=[CH:13][N:14]([C:24]=2[N:25]=1)[C@@H:15]1[O:23][C@H:20]([CH2:21][OH:22])[C@@H:18]([OH:19])[C@H:16]1[OH:17]>CN(C=O)C.CN(P(N(C)C)(N(C)C)=O)C.[Cu](Br)Br>[F:2][C:3]([F:5])([F:4])[C:8]1[N:9]=[C:10]([NH2:26])[C:11]2[N:12]=[CH:13][N:14]([C:24]=2[N:25]=1)[C@@H:15]1[O:23][C@H:20]([CH2:21][OH:22])[C@@H:18]([OH:19])[C@H:16]1[OH:17]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of trifluoromethylzinc bromide (1.308 g, 6.10 mmol) in DMF (25 mL) and HMPA (10 mL) was added to copper bromide (0.438 g, 3.05 mmol) and the resulting mixture was stirred for 30 min. 2-Iodoadenosine (0.800 g, 2.03 mmol) was added and the solution was warmed at 70° C. for 4 h. The solvents were evaporated and the residue was purified on silica gel with 10% methanol/chloroform to give 2-trifluoromethyladenosine in 63% yield. 2-Trifluoromethyladenosine was converted to IV by using in sequence the following procedures: Procedure A (58% yield), Procedure B (84% yield), Procedure C (51% yield), Procedure D (73% yield), Procedure E (75% yield), and Procedure F (53% yield): mp 173°-175° C.; 13NMR (Me2SO-d6) δ25.7, 31.8, 62.8, 82.1, 84.5, 119.8, 141.1, 148.3, 156.2; 1H NMR (Me2SO-d6) δ2.10 (m, 2 H), 2.40 (m, 2H), 3.51 (m, 2H), 4.13 (m, 1H), 4.88 (m, 1H), 6.25 (m, 1H), 7.85 (br.s, 2H), 8.54 (s, 1H); UV (H2O) λmax 259.5 nm (λ11300); FAB HRMS obsd (M+ +H) 304.0996, calcd for C11H12F3N5O2 304.1021.

Workup

customThe solvents were evaporated
customthe residue was purified on silica gel with 10% methanol/chloroform

Sources & evidence

ORD record: ord-cd6396301ca64dd5967bc19a27395ba4
Source dataset: uspto-grants-1991_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05013829

Reaction notes

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