Pyridine → Isotorabine

HRID 1662968Notes

Reaction equation

HRID 1662968 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26][Si](C(C)(C)C)(C)C)[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]3[O:14][C:15](=[O:17])[CH3:16])[C:6]=2[N:7]=1.N1C=CC=CC=1>C1COCC1>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][OH:26])[C@@H:18]([O:19][C:20](=[O:22])[CH3:21])[C@H:13]3[O:14][C:15](=[O:17])[CH3:16])[C:6]=2[N:7]=1

Participants

4

Reactant 2

HCID 1049PyridineHCID 576738995-Amino-3-(2',3'-di-O-acetyl, 5'-O-tert-butyl-dimethylsilanyl-beta-D-ribofuranosyl)-3H-thiazolo[4,5-d]pyrimidin-2-one

Product 1

HCID 11234476IsotorabineYield 100.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 92 (0.22 g, 0.44 mmol) in THF (5 mL) in a plastic vial was added HF/pyridine (0.70 mL). The reaction was stirred for 2 h, concentrated and purified by flash column chromatography (silica, MeOH/CHCl3: gradient=5-10%) to afford 0.17 g (100%) of the title compound as a white solid: mp 109-111° C.; 1H (400 MHz, d6-DMSO) δ 8.37 (s, 1H), 6.91 (s, 2H), 6.00 (m, 2H), 5.48 (t, J=6.0 Hz, 1H), 4.91 (t, J=6.0 Hz, 1H), 4.04 (dd, J=10.4, 6.0 Hz, 1H), 3.64 (m, 1H), 3.52 (m, 1H), 2.08 (s, 3H), 2.05 (s, 3H); MS (+)-ES [M+H]+ m/z 385.3. Elemental Analysis calc'd for C14H16N4O7S.0.5 CH3OH.0.2 CHCl3: C, 41.61; H, 4.32; N, 13.21; S 7.56. Found: C, 41.73; H, 4.29; N, 12.86; S, 7.33.

Workup

  1. concentrationconcentrated
  2. custompurified by flash column chromatography (silica, MeOH/CHCl3: gradient=5-10%)

Sources & evidence

ORD record
ord-868bcd281b9645d39e72744c6b4ff1d0
Source dataset
uspto-grants-2011_10
Patent number
US08034802B2

Reaction notes

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