Triphenylphosphine → 5-Amino-7-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethoxy)-3-(2',3',5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2-one

HRID 2102279Notes

Reaction equation

HRID 2102279 reaction equation
[NH2:1][C:2]1[NH:3][C:4](=[O:30])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26][C:27](=[O:29])[CH3:28])[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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:51][C:52]1[O:53][C:54](=[O:58])[O:55][C:56]=1[CH3:57].N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[NH2:1][C:2]1[N:3]=[C:4]([O:30][CH2:51][C:52]2[O:53][C:54](=[O:58])[O:55][C:56]=2[CH3:57])[C:5]2[S:10][C:9](=[O:11])[N:8]([C@@H:12]3[O:24][C@H:23]([CH2:25][O:26][C:27](=[O:29])[CH3:28])[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

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 105108784-(Hydroxymethyl)-5-methyl-1,3-dioxol-2-oneHCID 1354347855-amino-3-(2,3,5-tri-O-acetyl-beta-ribofuranosyl)thiazolo(4,5-d)pyrimidine-2,7-dione

Product 1

HCID 117862115-Amino-7-(5-methyl-2-oxo-[1,3]dioxol-4-ylmethoxy)-3-(2',3',5'-tri-O-acetyl-beta-D-ribofuranosyl)-thiazolo[4,5-d]pyrimidin-2-oneYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of triacetate 75 (1.55 g, 3.50 mmol) in THF (50 mL) at 0° C. was added polymer supported-triphenylphosphine (4.95 g, 10.50 mmol, Argonaut). To this mixture was added 4-hydroxymethyl-5-methyl-[1,3]dioxol-2-one (0.91 g, 7.00 mmol), prepared according to the procedure of Alepegiani, Syn. Comm., 22(9), 1277-82 (1992) Diethyl azodicarboxylate (0.73 ml, 4.60 mmol) was then added dropwise. The resulting mixture was stirred at room temperature for 48 h, filtered and washed with MeOH and CHCl3. The filtrate was concentrated and purified by flash column chromatography (silica, acetone/CHCl3=10-20%) to afford dioxolone derivative 85 (1.38 g, 71%) as white solid: 1H (400 MHz, d6-DMSO);δ 7.06 (s, 2H), 6.00 (d, J=4.0 Hz, 1H), 5.92 (dd, J=6.6, 4.4 Hz, 1H), 5.56 (t, J=6.4 Hz, 1H), 5.30 (s, 2H), 4.38 (dd, J=11.6, 3.6 Hz, 1H), 4.25 (t, J=3.6 Hz, 1H), 4.10 (q, J=6.0 Hz, 1H), 2.23 (s, 3H), 2.08 (s, 3H), 2.07 (s, 3H), 2.00 (s, 3H); MS (+)-ES [M+H]+ m/z 555.3. Elemental Analysis calc'd for C21H22N4O12S.Me2CO: C, 47.06; H, 4.61; N, 9.15; S, 5.23. Found: C, 47.25; H, 4.37; N, 9.53; S, 5.52.

Workup

  1. customprepared
  2. filtrationfiltered
  3. washwashed with MeOH and CHCl3
  4. concentrationThe filtrate was concentrated
  5. custompurified by flash column chromatography (silica, acetone/CHCl3=10-20%)

Sources & evidence

ORD record
ord-79870de2e0564719abc32c0fdca11701
Source dataset
uspto-grants-2009_08
Patent number
US07576068B2

Reaction notes

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