Potassium Phosphate, Tribasic → 6-(4-(1H-imidazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethyl-piperidin-4-yl)pyridazin-3-amine

HRID 1027175Notes

Reaction equation

HRID 1027175 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9](B(O)O)=[C:8]([O:15][CH3:16])[CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.Cl[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.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>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].O.O1CCOCC1>[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([C:18]3[N:23]=[N:22][C:21]([N:24]([CH3:35])[CH:25]4[CH2:30][C:29]([CH3:31])([CH3:32])[NH:28][C:27]([CH3:34])([CH3:33])[CH2:26]4)=[CH:20][CH:19]=3)=[C:8]([O:15][CH3:16])[CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2×HCID 86710567(4-(1H-imidazol-1-yl)-2-methoxyphenyl)boronic acid

Product 1

HCID 867105686-(4-(1H-imidazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethyl-piperidin-4-yl)pyridazin-3-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added (4-(1H-imidazol-1-yl)-2-methoxyphenyl)boronic acid (120 mg, 0.55 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine Intermediate 1-1 (156 mg, 0.55 mmol), potassium phosphate (351 mg, 1.65 mmol), Pd2(dba)3 (25.2 mg, 0.028 mmol), and SPhos (22.6 mg, 0.05 mmol), followed by addition of 1,4-dioxane (2 mL)/H2O (0.5 mL). The vial was purged with N2 for 10 minutes and the reaction mixture was heated at 100° C. in the microwave for 40 min. The reaction mixture was concentrated in vacuo and adjusted to pH 3 by 1 M HCl aqueous solution, then loaded on an SCX column. The column was washed with methanol and eluted with 2 N NH3 in methanol. The product-containing fractions were concentrated to afford 6-(4-(1H-imidazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethyl-piperidin-4-yl)pyridazin-3-amine (90 mg, MS: 421.4 [M+H+]).

Workup

  1. customThe vial was purged with N2 for 10 minutes
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. washThe column was washed with methanol
  4. washeluted with 2 N NH3 in methanol
  5. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-c3a425f939e147648a56026aa065aad3
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

Loading…