Imidazole → 4-Amino-1-((2R,4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-iodopyrimidin-2(1H)-one

HRID 500315Notes

Reaction equation

[I:1][C:2]1[C:3]([NH2:17])=[N:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.N1C=CN=C1.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>CN(C=O)C>[Si:23]([O:13][CH2:12][C@H:11]1[O:14][C@@H:7]([N:6]2[CH:15]=[C:2]([I:1])[C:3]([NH2:17])=[N:4][C:5]2=[O:16])[CH2:8][C@@H:9]1[OH:10])([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 5-iodo-2′-deoxycytidine (2.2 g, 6.23 mmol) in DMF (130 ml) was added imidazole (467 mg, 6.85 mmol). The mixture was cooled at 0° C. and tert-butyldimethylsilyl chloride (TBDMSCl) (1.33 g, 6.85 mmol) added over 5 minutes. After 18 h at room temperature, the volatiles were evaporated under reduced pressure and the residue purified by flash chromatography on silica gel with EtOAc:MeOH (95:5 to to 90:10) to give the expected product (39) (2.10 g, 72%) together with unreacted starting material (490 mg). 1H NMR (d6 DMSO) δ 0.11 (s, 3H, CH3), 0.12 (s, 3H, CH3), 0.89 (s, 9H, 3CH3), 1.90 (ddd, J=13.2, 7.7 and 5.7 Hz, 1H, HH-2′), 2.18 (ddd, J=13.2, 5.7 and 2.3 Hz, 1H, HH-2′), 3.72 (dd, J=11.5, 3.6 Hz, 1H, HH-5′), 3.80 (dd, J=11.5, 2.8 Hz, 1H, HH-5′), 3.86-3.89 (m, 1H, H-4′), 4.14-4.18 (m, 1H, H-3′), 5.22 (1H, d, J=4.1 Hz, OH), 6.09 (1H, dd, J=7.8, 5.8 Hz, H-1′), 6.60 (br s, 1H, NHH), 7.81 (br 9, 1H, NHH), 7.94 (s, 1H, H-6); MS (ES): m/z (%) (M+H) 468 (90%).

Workup

customthe volatiles were evaporated under reduced pressure
customthe residue purified by flash chromatography on silica gel with EtOAc:MeOH (95:5 to to 90:10)

Sources & evidence

ORD record: ord-2a935ecf5cdd4c7098cda2d6c9ec912a
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07771973B2

Reaction notes

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