1,2-Dimethoxyethane → 6-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

HRID 1027293

Reaktionsgleichung

Reaktionsgleichung von HRID 1027293
[CH3:1][O:2][C:3]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=[CH:5][C:4]=1[C:18]1[N:23]=[N:22][C:21]([N:24]([CH3:35])[CH:25]2[CH2:30][C:29]([CH3:32])([CH3:31])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]2)=[CH:20][CH:19]=1.Br[C:37]1[NH:38][CH:39]=[CH:40][N:41]=1.C([O-])([O-])=O.[Na+].[Na+].COCCOC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CCO>[NH:41]1[CH:40]=[CH:39][N:38]=[C:37]1[C:7]1[CH:6]=[CH:5][C:4]([C:18]2[N:23]=[N:22][C:21]([N:24]([CH3:35])[CH:25]3[CH2:26][C:27]([CH3:33])([CH3:34])[NH:28][C:29]([CH3:31])([CH3:32])[CH2:30]3)=[CH:20][CH:19]=2)=[C:3]([O:2][CH3:1])[CH:8]=1

Komponenten

8

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27732612-Bromo-1H-imidazoleHCID 867107236-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2×

Produkt 1

HCID 867107226-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amineAusbeute 45,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a microwave vial was added 6-(2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 9-3, 100 mg, 0.21 mmol), 2-bromo-1H-imidazole (61.2 mg, 0.42 mmol), Na2CO3 (44 mg, 0.42 mmol), and Pd(PPh3)2Cl2 (14 mg, 0.02 mmol), followed by DME (1 mL)/EtOH 0.25 mL)/(H2O (0.25 mL). The vial was purged with N2 for 10 min and the reaction mixture was heated at 150° C. in a microwave reactor for 20 min. The reaction mixture was filtered through celite and the filter cake was washed with EtOAc. The filtrate was concentrated in vacuo to give the crude product which was purified by silica gel chromotography (5%-15% MeOH/DCM) to afford 6-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (40 mg, MS: 421.3 [M+H+]).

Aufarbeitung

  1. customThe vial was purged with N2 for 10 min
  2. filtrationThe reaction mixture was filtered through celite
  3. washthe filter cake was washed with EtOAc
  4. concentrationThe filtrate was concentrated in vacuo
  5. customto give the crude product which
  6. customwas purified by silica gel chromotography (5%-15% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-547d5d0c91494a3eba24cf62eb4b2e9b
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08729263B2

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