Potassium Phosphate, Tribasic → HCID 86710695, compound

HRID 1027278Notes

Reaction equation

HRID 1027278 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][C:16]([CH2:19][CH:20]3[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)=[CH:17][CH:18]=2)=[C:9]([O:30][CH3:31])[CH:8]=1)(=O)=O.[NH:34]1[CH:38]=[C:37](B(O)O)[CH:36]=[N:35]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>[CH3:31][O:30][C:9]1[CH:8]=[C:7]([C:37]2[CH:38]=[N:34][NH:35][CH:36]=2)[CH:12]=[CH:11][C:10]=1[C:13]1[N:14]=[N:15][C:16]([CH2:19][CH:20]2[CH2:25][C:24]([CH3:26])([CH3:27])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 177502781H-Pyrazole-4-boronic acidHCID 86710696HCID 86710696, compound

Product 1

HCID 86710695HCID 86710695, compoundYield 99.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

To a microwave vial was added 3-methoxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenyl trifluoromethanesulfonate (160 mg, 0.33 mmol), 1H-pyrazol-4-ylboronic acid, (73.4 mg, 0.66 mmol), potassium phosphate (209 mg, 0.99 mmol), Pd2(dba)3 (30.1 mg, 0.03 mmol), and SPhos (26.9 mg, 0.06 mmol), followed by addition of 1,4-dioxane (2.6 mL)/H2O (0.7 mL). The vial was purged with N2 for 5 minutes and the reaction mixture was heated at 100° C. in the microwave for 1 h. 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 3-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazine (133 mg) MS [M+H+]=406.2.

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-ee0c9c4c98644739a1bafff47d2abb37
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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