Sodium Carbonate → (9S)-9-(4'-chloro-3'-fluorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1748107Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1748107
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[F:11].FC(F)(F)S(O[C:18]1[CH:23]=[CH:22][C:21]([C@H:24]2[C:29]3=[N:30][S:31](=[O:35])(=[O:34])[CH2:32][CH2:33][N:28]3[CH2:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CCO.O.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:18]2[CH:19]=[CH:20][C:21]([C@H:24]3[C:29]4=[N:30][S:31](=[O:35])(=[O:34])[CH2:32][CH2:33][N:28]4[CH2:27][CH2:26][CH2:25]3)=[CH:22][CH:23]=2)=[CH:4][C:3]=1[F:11]

Komponenten

8

Edukt 3

HCID 10340Sodium CarbonateHCID 27786564-Chloro-3-fluorophenylboronic AcidHCID 866636154-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenyl trifluoromethanesulfonate

Produkt 1

HCID 66748508(9S)-9-(4'-chloro-3'-fluorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideAusbeute 5,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Tetrakis(triphenylphosphine)palladium(0) (16.0 mg) was added to a mixture of (4-chloro-3-fluorophenyl)boronic acid (85.0 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenyl trifluoromethanesulfonate (100 mg) and sodium carbonate (51.4 mg) in EtOH (3 mL), water (1.5 mL) and DMF (dry) (2 mL). The mixture was stirred at 50° C. under nitrogen for 16 hr. Silica-gel was added and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) and concentrated. The residue was dissolved in MeCN/DMSO (1900/100 μM) and purified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA). The desired fractions were neutralized with sat. NaHCO3 aq., extracted with EtOAc and washed with brine. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (5.00 mg) as a white solid.

Aufarbeitung

  1. additionSilica-gel was added
  2. customthe volatiles were removed in vacuo
  3. customwas purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in MeCN/DMSO (1900/100 μM)
  6. custompurified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA)
  7. extractionextracted with EtOAc
  8. washwashed with brine
  9. customThe organic layer was separated
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-c5e9b9c757ac4c3594a9c58ee94daeb2
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09150591B2

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