1,4-Diazabicyclo(3.2.2)nonane → 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one

HRID 77404

Reaktionsgleichung

Reaktionsgleichung von HRID 77404
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1.[N:21]12[CH2:29][CH2:28][CH:25]([CH2:26][CH2:27]1)[NH:24][CH2:23][CH2:22]2.CC(C)([O-])C.[Na+].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:21]12[CH2:29][CH2:28][CH:25]([CH2:26][CH2:27]1)[N:24]([C:2]1[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=4)[N:8]([CH3:13])[C:9]3=[O:12])=[CH:4][CH:3]=1)[CH2:23][CH2:22]2

Komponenten

8

Edukt 4

HCID 3984071,4-Diazabicyclo(3.2.2)nonaneHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 699285487-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one2×

Produkt 1

HCID 513534447-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-oneAusbeute 35 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of 7-bromo-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one (Intermediate 24A) (50 mg, 0.143 mmol), 1,4-diazabicyclo[3.2.2]nonane (27.2 mg, 0.215 mmol), sodium t-butoxide (55.1 mg, 0.574 mmol), tris(dibenzylideneacetone)dipalladium(0) (13.13 mg, 0.014 mmol) and (+/−) BINAP (26.8 mg, 0.043 mmol) in degassed dioxane (1 mL) was heated to 85° C. under N2 in a sealed vessel overnight. Reaction mixture allowed to cool to room temperature, diluted with water and the product extracted into ethyl acetate. Organics washed several times with water, dried (MgSO4), filtered and then evaporated to dryness. The crude product was added to a silica gel column (25 g) and was eluted with 0-50% 2M ammonia in methanol in ethylacetate to afford 7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-3-(3-chlorophenyl)-2-methylisoquinolin-1(2H)-one (19.4 mg, 0.05 mmol).

Aufarbeitung

  1. customReaction mixture
  2. temperatureto cool to room temperature
  3. extractionthe product extracted into ethyl acetate
  4. dry with materialOrganics washed several times with water, dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. additionThe crude product was added to a silica gel column (25 g)
  8. washwas eluted with 0-50% 2M ammonia in methanol in ethylacetate

Quellen und Nachweise

ORD-Eintrag
ord-c1d1c04561374a87909533458de57e09
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841289B2

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