1-Hydroxybenzotriazole → rac-4-({2-[(1R,2R,4S)-bicyclo [2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidin-5-yl}carbonyl)thiomorpholine 1,1-dioxide

HRID 38795

Reaktionsgleichung

Reaktionsgleichung von HRID 38795
[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[O:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[C:12]([C:19](O)=[O:20])=[CH:11][N:10]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.[NH:44]1[CH2:49][CH2:48][S:47](=[O:51])(=[O:50])[CH2:46][CH2:45]1>CN(C)C=O>[C@H:1]12[CH2:7][C@H:4]([CH2:5][CH2:6]1)[CH2:3][C@H:2]2[O:8][C:9]1[N:14]=[C:13]([C:15]([F:18])([F:16])[F:17])[C:12]([C:19]([N:44]2[CH2:49][CH2:48][S:47](=[O:51])(=[O:50])[CH2:46][CH2:45]2)=[O:20])=[CH:11][N:10]=1

Komponenten

6

Edukt 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6484228Thiomorpholine 1,1-dioxideHCID 66720184rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid

Produkt 1

HCID 69813135rac-4-({2-[(1R,2R,4S)-bicyclo [2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidin-5-yl}carbonyl)thiomorpholine 1,1-dioxideAusbeute 59 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of rac-2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidine-5-carboxylic acid (55 mg) in N,N-dimethylformamide (5 mL) were added 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (70 mg) and 1-hydroxybenzotriazole (49 mg), followed by stirring at room temperature for 30 minutes. To the reaction mixture was added thiomorpholine 1,1-dioxide (49 mg), followed by stirring at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, and to the obtained residue was added water, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform-methanol=100:0 to 95:5). To the obtained residue was added ethanol (3 mL), followed by heating and dissolving, and then stirring at room temperature for 1 hour. The precipitated colorless solid was collected by filtration, washed with a small amount of ethanol, and then dried to obtain rac-4-({2-[(1R,2R,4S)-bicyclo[2.2.1]hept-2-yloxy]-4-(trifluoromethyl)pyrimidin-5-yl}carbonyl)thiomorpholine 1,1-dioxide (45 mg).

Aufarbeitung

  1. stirringby stirring at room temperature for 15 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionto the obtained residue was added water
  4. extractionfollowed by extraction with ethyl acetate
  5. washThe obtained organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (eluent: chloroform-methanol=100:0 to 95:5)
  9. additionTo the obtained residue was added ethanol (3 mL)
  10. temperatureby heating
  11. dissolutiondissolving
  12. stirringstirring at room temperature for 1 hour
  13. filtrationThe precipitated colorless solid was collected by filtration
  14. washwashed with a small amount of ethanol
  15. customdried

Quellen und Nachweise

ORD-Eintrag
ord-1062bc277c394436a27316aad430b4e3
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524727B2

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