Potassium Phosphate, Tribasic → HCID 86710573, compound

HRID 1027179Notes

Reaction equation

HRID 1027179 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]([N:19]([CH3:30])[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:31][CH3:32])[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>[CH3:32][O:31][C:9]1[CH:8]=[C:7]([C:38]2[CH:39]=[N:35][NH:36][CH:37]=2)[CH:12]=[CH:11][C:10]=1[C:13]1[N:14]=[N:15][C:16]([N:19]([CH3:30])[CH:20]2[CH2:21][C:22]([CH3:29])([CH3:28])[NH:23][C:24]([CH3:26])([CH3:27])[CH2:25]2)=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 177502781H-Pyrazole-4-boronic acidHCID 86710574HCID 86710574, compound

Product 1

HCID 86710573HCID 86710573, compound

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-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl trifluoromethanesulfonate (60 mg, 0.12 mmol), 1H-pyrazole-4-boronic acid (25.5 mg, 0.13 mmol), potassium phosphate (76 mg, 0.36 mmol), Pd2(dba)3 (6 mg, 5.9 umol), and SPhos (5 mg, 0.012 mmol), followed by addition of 1,4-dioxane (1 mL)/H2O (0.2 mL). The vial was purged with N2 for 10 minutes and the reaction mixture was heated at 100° C. in the microwave for one hour. The reaction mixture was concentrated in vacuo, and the crude product was adjusted to pH 3 using 1 M aqueous HCl, then loaded on an SCX column. The crude product was washed with methanol then eluted with 2 N ammonia in methanol. The product fractions were collected and dried to afford 6-(2-methoxy-4-(1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (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 crude product was washed with methanol
  4. washthen eluted with 2 N ammonia in methanol
  5. customThe product fractions were collected
  6. customdried

Sources & evidence

ORD record
ord-7d921408decc4fb6b38dfe87fb21cf65
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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