Potassium Phosphate, Tribasic → US10023592, Example 342

HRID 518522Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 518522
Br[C:2]1[CH:3]=[C:4]([NH:17][S:18]([CH2:21][CH3:22])(=[O:20])=[O:19])[CH:5]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[F:16])[CH:7]=1.[CH3:23][N:24]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[C:26]([CH3:39])[C:25]1=[O:40].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[CH:5]=[C:4]([NH:17][S:18]([CH2:21][CH3:22])(=[O:20])=[O:19])[CH:3]=[C:2]([C:28]2[CH:27]=[C:26]([CH3:39])[C:25](=[O:40])[N:24]([CH3:23])[CH:29]=2)[CH:7]=1

Komponenten

7

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 712703091,3-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydropyridin-2-oneHCID 118021931N-[3-bromo-5-(2,4-difluorophenoxy)phenyl]ethanesulfonamide

Produkt 1

HCID 118021789US10023592, Example 342Ausbeute 94 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A mixture of N-[3-bromo-5-(2,4-difluorophenoxyl)phenyl]ethanesulfonamide (70 mg, 0.17 mmol), 1,3-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (44 mg, 0.18 mmol), Pd(dppf)Cl2 (12 mg) and K3PO4 (92 mg, 0.42 mmol) in dioxane (1 mL) and water (133 uL) was purged with nitrogen, capped, and heated to 75° C. for 1 h. After the mixture was filtered through a short bed of celite, the filtrate was concentrated in vacuo and purified by silica gel column chromatography using a gradient of MeOH (0 to 10%) in DCM to afford the title compound (69 mg, 94%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13-1.22 (m, 3H) 2.07 (s, 3H) 3.08-3.20 (m, 2H) 3.50 (s, 3H) 6.65-6.70 (m, 1H) 6.92-6.96 (m, 1H) 7.05-7.10 (m, 1H) 7.12-7.19 (m, 1H) 7.28-7.37 (m, 1H) 7.47-7.55 (m, 1H) 7.56-7.59 (m, 1H) 7.87-7.95 (m, 1H) 9.76-9.94 (m, 1H). LCMS (M+H)+=435.

Aufarbeitung

  1. customwas purged with nitrogen
  2. customcapped
  3. filtrationAfter the mixture was filtered through a short bed of celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. custompurified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-42cbdbee0dce4d0e8a790eef189f2af0
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115114B2

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