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Trifluoroacetic acid → 9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-7-(hydroxymethyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

HRID 2201262
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2201262
FC(F)(F)C(O)=O.[Si]([O:15][CH2:16][CH:17]1[CH2:24][CH:23]([C:25]2[S:26][CH:27]=[C:28]([Cl:30])[N:29]=2)[C:22]2[N:18]1[C:19]([C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=1)=[C:20]1[C:34](=[O:35])[N:33]([CH3:36])[C:32](=[O:37])[N:31]([CH3:38])[C:21]1=2)(C(C)(C)C)(C)C>CO.O>[Cl:30][C:28]1[N:29]=[C:25]([CH:23]2[C:22]3[N:18]([C:19]([C:39]4[CH:44]=[CH:43][CH:42]=[C:41]([F:45])[CH:40]=4)=[C:20]4[C:34](=[O:35])[N:33]([CH3:36])[C:32](=[O:37])[N:31]([CH3:38])[C:21]4=3)[CH:17]([CH2:16][OH:15])[CH2:24]2)[S:26][CH:27]=1
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Komponenten

5

Edukt 2

HCID 6422Trifluoroacetic acid2×HCID 867235027-(((tert-Butyldimethylsilyl)oxy)methyl)-9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

Produkt 1

HCID 771076329-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-7-(hydroxymethyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887
Methanol
Lösungsmittel
HCID 962WaterLösungsmittel2×

Versuchsvorschrift

Trifluoroacetic acid (2 mL, 26.0 mmol) was added to a solution of 7-(((tert-butyldimethylsilyl)oxy)methyl)-9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione (570 mg, 0.991 mmol) in methanol (20 mL) and water (3 mL). The mixture stirred at room temperature 20 mins. Further portions of water (1 mL) and trifluoroacetic acid (1 mL) were added and the mixture stirred for a further 3 hours. The reaction was quenched with saturated NaHCO3(aq) and extracted with chloroform (3×). The combined organic extracts were passed through a hydrophobic frit and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-100% EtOAc/hexane afforded the title compounds as a mixture of diastereomers.

Aufarbeitung

  1. stirringthe mixture stirred for a further 3 hours
  2. customThe reaction was quenched with saturated NaHCO3(aq)
  3. extractionextracted with chloroform (3×)
  4. customevaporated under vacuum
  5. customPurification by chromatography on silica
  6. washeluting with 0-100% EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-2be1fd51d0eb446d9e04afea55e85d65
Quelldatensatz
uspto-grants-2016_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09359381B2

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