Dimethylformamide → 1-Azabicyclo[3.3.1]non-5-ylmethyl(5-phenyl-1,3-thiazol-4-yl)carbamate fumarate

HRID 383956

Reaktionsgleichung

Reaktionsgleichung von HRID 383956
[C:1]1([C:7]2[S:11][CH:10]=[N:9][C:8]=2C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:15]12[CH2:23][C:19]([CH2:24]O)([CH2:20][CH2:21][CH2:22]1)[CH2:18][CH2:17][CH2:16]2.C[N:27]([CH:29]=[O:30])C.[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35]>C1(C)C=CC=CC=1.CCO.O.C(Cl)(Cl)Cl>[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35].[N:15]12[CH2:23][C:19]([CH2:24][N:27]([C:8]3[N:9]=[CH:10][S:11][C:7]=3[C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:29](=[O:30])[OH:35])([CH2:18][CH2:17][CH2:16]1)[CH2:20][CH2:21][CH2:22]2

Komponenten

9

Edukt 4

HCID 6228DimethylformamideHCID 444972Fumaric AcidHCID 9448135-phenyl-1,3-thiazole-4-carboxylic AcidHCID 19795980{1-Azabicyclo[3.3.1]nonan-5-yl}methanol

Produkt 1

HCID 685935651-Azabicyclo[3.3.1]non-5-ylmethyl(5-phenyl-1,3-thiazol-4-yl)carbamate fumarate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 702EthanolLösungsmittel2×HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel2×HCID 6212ChloroformLösungsmittel

Versuchsvorschrift

To a solution of 5-phenyl-1,3-thiazole-4-carboxylic acid (385 mg) in toluene (5 mL) was added TEA (314 μL) at room temperature. Next, DPPA(486 μL) was added dropwise, followed by stirring at the same temperature for 30 minutes. After stirring at 90° C. for 5 minutes, a mixture of 1-azabicyclo[3.3.1]non-5-yl methanol (291 mg), DMF (1 mL), and toluene (4 mL) was added thereto, followed by stirring at 90° C. for 30 minutes. The reaction mixture was cooled to room temperature, and CHCl3 and water were then added thereto to separate the organic layer. The organic layer was washed with water and brine in this order, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH:aqueous ammonia). The collected fraction was concentrated under reduced pressure, followed by addition of 4 M HCl/EtOAc and concentration under reduced pressure. To the residue were added EtOAc and water to separate the aqueous layer. The aqueous layer was neutralized with NaHCO3 and extracted with CHCl3. The organic layer was washed with water and brine in this order, dried over MgSO4, and then concentrated under reduced pressure to obtain a tacky substance (129 mg). This was dissolved in EtOH, followed by addition of a solution of fumaric acid (40 mg) in EtOH and concentrated under reduced pressure to obtain 1-azabicyclo[3.3.1]non-5-ylmethyl(5-phenyl-1,3-thiazol-4-yl)carbamate fumarate (161 mg) as a colorless amorphous fluorescent substance.

Aufarbeitung

  1. stirringAfter stirring at 90° C. for 5 minutes
  2. additionwas added
  3. stirringby stirring at 90° C. for 30 minutes
  4. customto separate the organic layer
  5. washThe organic layer was washed with water and brine in this order
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by medium-pressure preparative liquid chromatography (silica gel, YAMAZEN YFLC WPrep2XY, CHCl3:MeOH:aqueous ammonia)
  9. concentrationThe collected fraction was concentrated under reduced pressure
  10. additionfollowed by addition of 4 M HCl/EtOAc and concentration under reduced pressure
  11. additionTo the residue were added EtOAc and water
  12. customto separate the aqueous layer
  13. extractionextracted with CHCl3
  14. washThe organic layer was washed with water and brine in this order
  15. dry with materialdried over MgSO4
  16. concentrationconcentrated under reduced pressure
  17. customto obtain a tacky substance (129 mg)
  18. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-af73b1d9e77c465bb276a55c3d4aab8a
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367696B2

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