Reaktion #711746

Reaktionsgleichung

HCl

dioxane

(R)-6-(3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)-5-(3-chlorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

4-chlorothiazole-2-carbaldehyde

Intermediate H

4-chlorothiazole-2-carbaldehyde

bismuth triflate

HCl

dioxane

→

title compound

(8R)-5-(3-Chlorophenyl)-10-(4-chlorothiazol-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-7,8-dihydro-1H-pyrimido[4′,5′:3,4]pyrrolo[2,1-c][1,4]oxazine-2,4(3H,10H)-dione

Lösungsmittel

ethanol

EtOAc

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction
2. 2
   TemperaturThe mixture was cooled to room temperature
3. 3
   SonstigeThe phases were separated
4. 4
   Extraktionthe aqueous phase extracted with EtOAc (3×30 ml)
5. 5
   WaschenThe combined organic extracts were washed with saturated NaHCO3(aq) (20 ml), water (20 ml) and brine (20 ml)
6. 6
   Trocknendried over sodium sulfate
7. 7
   Sonstigeevaporated under vacuum
8. 8
   SonstigePurification by chromatography on silica
9. 9
   Wascheneluting with 10-70% EtOAc/hexane

Vorschrift

HCl in dioxane (0.654 ml, 2.61 mmol) was added to a suspension of (R)-6-(3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)-5-(3-chlorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (250 mg, 0.523 mmol), 4-chlorothiazole-2-carbaldehyde (Intermediate H) (85 mg, 0.575 mmol) and bismuth triflate (103 mg, 0.157 mmol) in anhydrous ethanol (4 ml) and the mixture heated at 50° C. for 36 hours. Further portions of HCl in dioxane (0.654 ml, 2.61 mmol) were added as necessary to allow the reaction to run to completion. The mixture was cooled to room temperature and diluted with EtOAc (50 ml) and water (20 ml). The phases were separated and the aqueous phase extracted with EtOAc (3×30 ml). The combined organic extracts were washed with saturated NaHCO3(aq) (20 ml), water (20 ml) and brine (20 ml), dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 10-70% EtOAc/hexane afforded the title compound as a mixture of diastereomers.

Quelle