Nitrogen → US10023592, Example 15

HRID 518273Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 518273
N#N.Br[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[O:14])[N:6]([CH3:15])[CH:5]=1.[CH2:16]([NH:23][S:24]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:32]=1[O:33][CH3:34])(=[O:26])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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]>[CH2:16]([NH:23][S:24]([C:27]1[CH:28]=[C:29]([C:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:14])[N:6]([CH3:15])[CH:5]=2)[CH:30]=[CH:31][C:32]=1[O:33][CH3:34])(=[O:26])=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Komponenten

7

Edukt 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 3118584-Bromo-2-methylisoquinolin-1(2H)-oneHCID 44119816(3-(N-Benzylsulfamoyl)-4-methoxyphenyl)boronic acid

Produkt 1

HCID 118021549US10023592, Example 15Ausbeute 58,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

For about 3 min, N2 was bubbled through the mixture of 4-bromo-2-methylisoquinolin-1(2H)-one (56 mg, 0.24 mmol), [3-(benzylsulfamoyl)-4-methoxyphenyl]boronic acid (83 mg, 0.26 mmol), aqueous 2M Na2CO3 (0.375 mL) and Pd(dppf)Cl2 (9 mg, 0.001 mmol) in dioxane (1.5 mL) which was then microwaved at 120° C. for 1 h and then filtered through a plug of anhydrous Na2SO4 using ethyl acetate to transfer and rinse. Silica gel chromatography, eluting with 0-60% EA in hexane over 6 min and continuing 60% isocratic EA gave the title compound (60 mg, 0.14 mmol) as a white solid in 58% yield. 1H NMR (400 MHz, DMSO-d6) δ 3.57 (s, 3 H), 3.89 (s, 3H), 4.11 (d, J=6.32 Hz, 2H), 7.16-7.23 (m, 6H), 7.34 (d, J=8.08 Hz, 1H), 7.47 (s, 1H), 7.53-7.59 (m, 2H), 7.65 (d, J=2.27 Hz, 1H), 7.72-7.77 (m, 1H), 7.94 (t, J=6.32 Hz, 1H), 8.34 (d, J=7.33 Hz, 1H). LCMS (M+H)+ 435.

Aufarbeitung

  1. customwas then microwaved at 120° C. for 1 h
  2. filtrationfiltered through a plug of anhydrous Na2SO4
  3. washrinse
  4. washSilica gel chromatography, eluting with 0-60% EA in hexane over 6 min

Quellen und Nachweise

ORD-Eintrag
ord-dbdc674e672c48af8795bc8772f3fe2f
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09115114B2

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