Citric Acid → N-(methylsulfonyl)-4-{[6-(trifluoromethyl)pyridin-3-yl]methoxy}benzamide formate salt

HRID 512023

Reaktionsgleichung

Reaktionsgleichung von HRID 512023
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][CH:3]=1.[F:12][C:13]([F:23])([F:22])[C:14]1[N:19]=[CH:18][C:17]([CH2:20]O)=[CH:16][CH:15]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[Li+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[CH3:58][S:59]([NH2:62])(=[O:61])=[O:60].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH:6]([OH:8])=[O:7].[CH3:58][S:59]([NH:62][C:6](=[O:8])[C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:20][C:17]2[CH:18]=[N:19][C:14]([C:13]([F:23])([F:22])[F:12])=[CH:15][CH:16]=2)=[CH:11][CH:10]=1)(=[O:61])=[O:60]

Komponenten

10

Edukt 7

HCID 311Citric AcidHCID 3939Lithium HydroxideHCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 36138956-(Trifluoromethyl)pyridine-3-methanol

Produkt 1

HCID 86682565N-(methylsulfonyl)-4-{[6-(trifluoromethyl)pyridin-3-yl]methoxy}benzamide formate salt

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
30 °C

Versuchsvorschrift

To methyl 4-hydroxybenzoate (22.8 mg, 0.15 mmol) and [6-(trifluoromethyl)pyridin-3-yl]methanol (22.1 mg, 0.125 mmol) in DCM (1 mL) was added N,N,N′N′-tetramethylazodicarboxylate (43 mg) and polymer supported triphenylphosphine (3 mmol/g, 125 mg, 0.375 mmol). The reaction was shaken at 30° C. for 16 hours, filtered, diluted with aqueous citric acid solution (2.5%, 1 mL) and extracted with DCM (3×1 mL). The combined organics were concentrated in vacuo. The resulting crude residue was dissolved in THF (0.625 mL), treated with aqueous lithium hydroxide solution (2 M, 0.625 mL, 1.25 mmol) and the mixture shaken at 50° C. for 16 hours. The solvent was removed in vacuo, the residue dissolved in aqueous citric acid solution (4 M, 0.4 mL, 1.6 mmol) and extracted with EtOAc (3×1 mL), dried over sodium sulfate, filtered and the solvent removed in vacuo. To the resulting crude residue DCM (1 mL), methanesulphonamide (12 mg, 0.126 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI) (72 mg, 0.377 mmol) and DMAP (23 mg, 0.188 mmol) was added and the mixture was shaken at 30° C. for 16 hours. The solvent was removed under reduced pressure and the resulting crude product was purified by preparative HPLC to afford the title compound.

Aufarbeitung

  1. filtrationfiltered
  2. additiondiluted with aqueous citric acid solution (2.5%, 1 mL)
  3. extractionextracted with DCM (3×1 mL)
  4. concentrationThe combined organics were concentrated in vacuo
  5. dissolutionThe resulting crude residue was dissolved in THF (0.625 mL)
  6. stirringthe mixture shaken at 50° C. for 16 hours
  7. customThe solvent was removed in vacuo
  8. extractionextracted with EtOAc (3×1 mL)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent removed in vacuo
  12. stirringthe mixture was shaken at 30° C. for 16 hours
  13. customThe solvent was removed under reduced pressure
  14. customthe resulting crude product was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-0fbba13ecb0e4828b4193f515b156922
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102621B2

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