Potassium Phosphate, Tribasic → HCID 86710664, compound

HRID 1027255Notes

Reaction equation

HRID 1027255 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]([C:15]2[N:16]=[N:17][C:18]([N:21]([CH3:32])[CH:22]3[CH2:27][C:26]([CH3:29])([CH3:28])[NH:25][C:24]([CH3:31])([CH3:30])[CH2:23]3)=[CH:19][CH:20]=2)[CH:8]=1)(=O)=O.[NH:35]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36]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>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([C:38]2[CH:39]=[N:35][NH:36][CH:37]=2)=[CH:8][C:9]=1[C:15]1[N:16]=[N:17][C:18]([N:21]([CH3:32])[CH:22]2[CH2:23][C:24]([CH3:30])([CH3:31])[NH:25][C:26]([CH3:29])([CH3:28])[CH2:27]2)=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 177502781H-Pyrazole-4-boronic acidHCID 86710665HCID 86710665, compound

Product 1

HCID 86710664HCID 86710664, compoundYield 80.8%

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-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl trifluoromethanesulfonate (100 mg, 0.20 mmol), 1H-pyrazol-4-ylboronic acid (33.4 mg, 0.30 mmol), potassium phosphate (127 mg, 0.60 mmol), Pd2(dba)3 (18.22 mg, 0.02 mmol), and SPhos (16.4 mg, 0.04 mmol), followed by addition of 1,4-dioxane (1.6 mL)/H2O (0.4 mL). The vial was purged with N2 for 5 minutes and the reaction mixture was heated at 100° C. in the microwave for 1 hour. The reaction mixture was concentrated in vacuo. The crude material was adjusted to pH 3 using 1 M HCl aqueous solution and loaded on 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 6-(2-methoxy-5-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (68 mg) MS [M+H+]=421.3.

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-b349cb62dbb345608bafbdf0e0ac674e
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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