Sodium Carbonate → Ethanesulfonic acid [5-(8-chloro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amide

HRID 1774844Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1774844
C([O-])([O-])=O.[Na+].[Na+].[Cl:7][C:8]1[CH:9]=[C:10](B2OC(C)(C)C(C)(C)O2)[CH:11]=[C:12]2[C:17]=1[N:16]([CH3:18])[C:15](=[O:19])[CH2:14][CH2:13]2.Br[C:30]1[CH:31]=[C:32]([CH2:36][NH:37][S:38]([CH2:41][CH3:42])(=[O:40])=[O:39])[CH:33]=[N:34][CH:35]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:7][C:8]1[CH:9]=[C:10]([C:30]2[CH:31]=[C:32]([CH2:36][NH:37][S:38]([CH2:41][CH3:42])(=[O:39])=[O:40])[CH:33]=[N:34][CH:35]=2)[CH:11]=[C:12]2[C:17]=1[N:16]([CH3:18])[C:15](=[O:19])[CH2:14][CH2:13]2

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 58215658HCID 58215658, VerbindungHCID 722080468-Chloro-1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-YL)-3,4-dihydro-1H-quinolin-2-one

Produkt 1

HCID 86679189Ethanesulfonic acid [5-(8-chloro-1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amideAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumKatalysatorHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Under argon protection, bis(triphenylphosphine)palladium(II)chloride (4 mg, 0.05 mmol) followed by 1 N aqueous Na2CO3 solution (1 mL), was added to a solution of 8-chloro-1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (160 mg, 0.5 mmol) and ethanesulfonic acid (5-bromo-pyridin-3-ylmethyl)-amide (intermediate A-11, 158 mg, 0.6 mmol) in DMF (3 mL). The resulting reaction mixture was then heated in a microwave at 110° C. for 45 min. After cooling to room temperature, the reaction mixture was diluted with EtOAc (5 mL) and poured into a satd. aq. solution of NaHCO3 (10 mL). The aqueous layer was extracted with EtOAc (3×5 mL). Combined organics were washed with water and brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give title compound (65 mg, 45%) as a white solid. MS: 394.1 (M+H+)+.

Aufarbeitung

  1. customThe resulting reaction mixture
  2. temperatureAfter cooling to room temperature
  3. additionpoured into a satd
  4. extractionThe aqueous layer was extracted with EtOAc (3×5 mL)
  5. washCombined organics were washed with water and brine (20 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a crude product which
  10. customwas then purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d36980d2985f457faaa1528df1d38b6a
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260408B2

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