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

Reaction equation

HRID 1027293 reaction equation
[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

Participants

8

Reactant 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×

Product 1

HCID 867107226-(4-(1H-imidazol-2-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amineYield 45.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

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+]).

Workup

  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)

Sources & evidence

ORD record
ord-547d5d0c91494a3eba24cf62eb4b2e9b
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Linked notes

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