6-Bromo-N-methylnicotinamide → N-Methyl-6-[7-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl]-nicotinamide

HRID 467578

Reaktionsgleichung

Reaktionsgleichung von HRID 467578
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:22]=[CH:21][C:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:14]=3[CH:13]=2)[CH2:8]1.CC(C)([O-])C.[Na+].Br[C:30]1[CH:39]=[CH:38][C:33]([C:34]([NH:36][CH3:37])=[O:35])=[CH:32][N:31]=1>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:37][NH:36][C:34](=[O:35])[C:33]1[CH:38]=[CH:39][C:30]([N:18]2[CH2:19][CH2:20][C:14]3[CH:13]=[C:12]([N:9]4[CH2:10][CH2:11][C@H:7]([N:3]5[CH2:4][CH2:5][CH2:6][C@@H:2]5[CH3:1])[CH2:8]4)[CH:22]=[CH:21][C:15]=3[CH2:16][CH2:17]2)=[N:31][CH:32]=1

Komponenten

6

Edukt 3

HCID 230921426-Bromo-N-methylnicotinamideHCID 23676156Sodium t-butoxideHCID 546701937-((2S,3'S)-2-Methyl-1,3'-bipyrrolidinyl-1'-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine

Produkt 1

HCID 54670196N-Methyl-6-[7-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl]-nicotinamideAusbeute 92,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

7-((2S,3′S)-2-Methyl-1,3′-bipyrrolidinyl-1′-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine (150 mg, 0.50 mmol) was added to a mixture of tris(dibenzylideneacetone)-dipalladium (6.88 mg, 0.007), R-BINAP (22.5 mg, 0.022 mmol), sodium tert-butoxide (69.8 mg, 0.72 mmol) and 6-bromo-N-methyl-nicotinamide (118 mg, 0.55 mmol) in 6 mL of toluene and the mixture was degassed (vacuum, 3×). The reaction mixture was heated at 85° C. for 17 h, and then it was partitioned between ethyl acetate and water. The aqueous phase washed with ethyl acetate and then the organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated to leave 200 mg of an oil.

Aufarbeitung

  1. customthe mixture was degassed (vacuum, 3×)
  2. customit was partitioned between ethyl acetate and water
  3. washThe aqueous phase washed with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-0144bbb5c2c44ed287786531d85ff0f2
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623877B2

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