Potassium Phosphate, Tribasic → HCID 86710663, compound

HRID 1027254Notes

Reaction equation

HRID 1027254 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][C:4]=1B1OC(C)(C)C(C)(C)O1.Cl[C:20]1[N:25]=[N:24][C:23]([N:26]([CH3:37])[CH:27]2[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]2)=[CH:22][CH:21]=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>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][C:4]=1[C:20]1[N:25]=[N:24][C:23]([N:26]([CH3:37])[CH:27]2[CH2:32][C:31]([CH3:33])([CH3:34])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]2)=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 722194914-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2×

Product 1

HCID 86710663HCID 86710663, compoundYield 82.8%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (400 mg, 1.60 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 1-1, 452 mg, 1.60 mmol), potassium phosphate (1.4 g, 6.40 mmol), Pd2(dba)3 (146 mg, 0.16 mmol), and SPhos (65.7 mg, 0.16 mmol), followed by addition of 1,4-dioxane (4 mL)/H2O (0.8 mL). The vial was purged with N2 for 5 minutes and the reaction mixture was heated at 100° C. in the microwave for 2 h. The reaction mixture was concentrated in vacuo. The crude material was adjusted to pH 3 using 12 M HCl aqueous solution and loaded onto an SCX column. The crude material was washed with methanol then eluted with 2 N ammonia in methanol. The product-containing fractions were concentrated to afford 4-methoxy-3-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol (491 mg) MS [M+H+]=371.2.

Workup

  1. customThe vial was purged with N2 for 5 minutes
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. washThe crude material was washed with methanol
  4. washthen eluted with 2 N ammonia in methanol
  5. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-8283784b11f74bc88a39078c879d89f2
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

Loading…