Hydrochloric Acid → (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

HRID 624564Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 624564
Cl.O1CCOCC1.[Si]([O:15][CH2:16][C@H:17]([OH:39])[CH2:18][N:19]1[C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=2)=[C:26]2[C:21]([N:22]([CH3:38])[C:23](=[O:37])[N:24]([CH3:36])[C:25]2=[O:35])=[CH:20]1)(C(C)(C)C)(C)C.[Cl:40][C:41]1[N:42]=[C:43]([CH:46]=O)[S:44][CH:45]=1.[O-]S(C(F)(F)F)(=O)=O.[Bi+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>C(O)C.CCOC(C)=O.O>[Cl:34][C:30]1[CH:29]=[C:28]([C:27]2[N:19]3[C:20]([CH:46]([C:43]4[S:44][CH:45]=[C:41]([Cl:40])[N:42]=4)[O:39][C@@H:17]([CH2:16][OH:15])[CH2:18]3)=[C:21]3[N:22]([CH3:38])[C:23](=[O:37])[N:24]([CH3:36])[C:25](=[O:35])[C:26]=23)[CH:33]=[CH:32][CH:31]=1

Komponenten

9

Edukt 5

HCID 313Hydrochloric Acid2×HCID 312751,4-Dioxane2×HCID 9917655Bi(OTf)3HCID 451217834-Chloro-1,3-thiazole-2-carbaldehyde2×HCID 86722888(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

Produkt 1

HCID 86722889(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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

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.

Aufarbeitung

  1. customthe reaction
  2. temperatureThe mixture was cooled to room temperature
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted with EtOAc (3×30 ml)
  5. washThe combined organic extracts were washed with saturated NaHCO3(aq) (20 ml), water (20 ml) and brine (20 ml)
  6. dry with materialdried over sodium sulfate
  7. customevaporated under vacuum
  8. customPurification by chromatography on silica
  9. washeluting with 10-70% EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-4825bee7d5a7451fb76181b1e8e331cc
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303035B2

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