Potassium Carbonate → 5-amino-3-[(2R,3R,5S)-5-(1-hydroxypropyl)-3-prop-2-enyloxolan-2-yl]-6H-[1,3]thiazolo[4,5-d]pyrimidine-2,7-dione

HRID 60735Notes

Reaction equation

HRID 60735 reaction equation
C([O:9][CH:10]([C@@H:13]1[CH2:17][C@@H:16]([CH2:18][CH:19]=[CH2:20])[C@H:15]([N:21]2[C:25]3[N:26]=[C:27]([NH2:31])[NH:28][C:29](=[O:30])[C:24]=3[S:23][C:22]2=[O:32])[O:14]1)[CH2:11][CH3:12])(=O)C1C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].[NH4+].[Cl-]>CO>[CH2:18]([C@@H:16]1[CH2:17][C@@H:13]([CH:10]([OH:9])[CH2:11][CH3:12])[O:14][C@H:15]1[N:21]1[C:25]2[N:26]=[C:27]([NH2:31])[NH:28][C:29](=[O:30])[C:24]=2[S:23][C:22]1=[O:32])[CH:19]=[CH2:20]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 1371087171-[(2S,4R,5R)-4-allyl-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]propyl benzoate2×

Product 1

HCID 1371087595-amino-3-[(2R,3R,5S)-5-(1-hydroxypropyl)-3-prop-2-enyloxolan-2-yl]-6H-[1,3]thiazolo[4,5-d]pyrimidine-2,7-dioneYield 32.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-[(2S,4R,5R)-4-allyl-5-(5-amino-2,7-dioxo-6H-thiazolo[4,5-d]pyrimidin-3-yl)tetrahydrofuran-2-yl]propyl benzoate (compound 26f, 800 mg, 1.75 mmol) in methanol (25 mL) was added K2CO3 (483 mg, 3.5 mmol). After being stirred at room temperature for 12 hours, the reaction was diluted by saturated NH4Cl solution and extracted with DCM. The organic layers were combined and concentrated in vacuo. The residue was purified by preparative HPLC to afford 200 mg of 3-[(2R,3R,5S)-3-allyl-5-(1-hydroxypropyl)tetrahydrofuran-2-yl]-5-amino-6H-thiazolo[4,5-d]pyrimidine-2,7-dione (Example 26). 100 mg of Example 26 was further separated by supercritical fluid chromatography (SFC) to afford 32.0 mg of Example 26-A and 30.8 mg of Example 26-B as white solid.

Workup

  1. extractionextracted with DCM
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-fbbab511873f42c28a60ff46bb78a2a8
Source dataset
uspto-grants-2016_09
Patent number
US09441008B2

Reaction notes

Loading…